System and method for decision support

ABSTRACT

Systems and methods are provided to determine a time to provide guidance to a user regarding management of a physiologic condition such as diabetes. The determination may be based upon a model or pattern. The time to deliver guidance may be calculated to be useful to a user in the management of a glucose concentration level.

REFERENCE TO RELATED APPLICATION

Any and all priority claims identified in the Application Data Sheet, orany correction thereto, are hereby incorporated by reference under 37CFR 1.57. This application is a continuation of U.S. application Ser.No. 16/269,480, filed on Feb. 6, 2019, which claims the benefit of U.S.Provisional Application No. 62/628,895, filed on Feb. 9, 2018. Each ofthe aforementioned applications is incorporated by reference herein inits entirety, and each is hereby expressly made a part of thisspecification.

TECHNICAL FIELD

The present development relates generally to medical devices such asanalyte sensors, including systems and methods for using the same toprovide support for treatment decision-making.

BACKGROUND

Diabetes is a metabolic condition relating to the production or use ofinsulin by the body. Insulin is a hormone that allows the body to useglucose for energy, or store glucose as fat.

When a person eats a meal that contains carbohydrates, the food isprocessed by the digestive system, which produces glucose in theperson's blood. Blood glucose can be used for energy or stored as fat.The body normally maintains blood glucose levels in a range thatprovides sufficient energy to support bodily functions and avoidsproblems that can arise when glucose levels are too high, or too low.Regulation of blood glucose levels depends on the production and use ofinsulin, which regulates the movement of blood glucose into cells.

When the body does not produce enough insulin, or when the body isunable to effectively use insulin that is present, blood sugar levelscan elevate beyond normal ranges. The state of having a higher thannormal blood sugar level is called “hyperglycemia.” Chronichyperglycemia can lead to a number of health problems, such ascardiovascular disease, cataract and other eye problems, nerve damage(neuropathy), and kidney damage. Hyperglycemia can also lead to acuteproblems, such as diabetic ketoacidosis—a state in which the bodybecomes excessively acidic due to the presence of blood glucose andketones, which are produced when the body cannot use glucose. The stateof having lower than normal blood glucose levels is called“hypoglycemia.” Severe hypoglycemia can lead to acute crises that canresult in seizures or death.

A diabetes patient can receive insulin to manage blood glucose levels.Insulin can be received, for example, through a manual injection with aneedle. Wearable insulin pumps are also available. Diet and exercisealso affect blood glucose levels.

Diabetes conditions are sometimes referred to as “Type 1” and “Type 2”.A Type 1 diabetes patient is typically able to use insulin when it ispresent, but the body is unable to produce sufficient amounts ofinsulin, because of a problem with the insulin-producing beta cells ofthe pancreas. A Type 2 diabetes patient may produce some insulin, butthe patient has become “insulin resistant” due to a reduced sensitivityto insulin. The result is that even though insulin is present in thebody, the insulin is not sufficiently used by the patient's body toeffectively regulate blood sugar levels.

This Background is provided to introduce a brief context for the Summaryand Detailed Description that follow. This Background is not intended tobe an aid in determining the scope of the claimed subject matter nor beviewed as limiting the claimed subject matter to implementations thatsolve any or all of the disadvantages or problems presented above.

SUMMARY

This document discusses, among other things, systems and methods todetermine a time for delivery or determination of decision-supportguidance for a patient or caregiver.

An example (e.g., “Example 1”) of subject matter (e.g., a method orsystem) may include measuring, determining, or receiving a firstreal-time datum associated with a patient, determining a state thepatient is in using at least in part a model and the first real-timedatum, determining a guidance message, wherein the guidance message isbased at least in part on the determined state, and providing thedetermined personalized guidance message through a user interface at atime calculated to enable intervention prior to a transition to anundesirable physiologic state.

In Example 2, the subject matter of Example 1 may be configured suchthat determining a guidance message is further based on a timing of thedetermining the guidance message or a time associated with thedetermined state.

In Example 3, the subject matter of Example 1 or 2 may be configuredsuch that the model includes a state indicative of a convenience oravailability of the patient to participate in an intervention.

In Example 4, the subject matter of any one or any combination ofExamples 1-3 may be configured such that the guidance message is basedat least in part on a projected transition to the undesirablephysiologic state.

In Example 5, the subject matter of any one or any combination ofExamples 1-4 may be configured such that the guidance message is basedat least in part on a determination that a projected transition from apresent state to a projected state is a low-probability transition.

In Example 6, the subject matter of any one or any combination ofExamples 1-5 may be configured such that the model includes a patientphysiology model and determining a state the patient is in is based atleast on applying the first real-time datum to the patient physiologymodel.

In Example 7, the subject matter of any one or any combination ofExamples 1-6 may be configured such that the model includes a behaviormodel.

In Example 8, the subject matter of any one or any combination ofExamples 1-7 may be configured such that a behavior model is based on amachine-learned characteristic of the patient, the machine-learnedcharacteristic being based on a behavioral or contextual pattern.

In Example 9, the subject matter of any one or any combination ofExamples 1-8 may be configured such that the behavior model is based ona set of one or more steps determined to be likely to be performed bythe patient.

In Example 10, the subject matter of any one or any combination ofExamples 1-9 may be configured such that a behavior model is based on aset of one or more objectives determined to be likely attainable by thepatient.

In Example 11, the subject matter of any one or any combination ofExamples 1-10 may be configured such that the model includes a behaviormodel that is a pattern.

In Example 12, the subject matter of any one or any combination ofExamples 1-11 may be configured such that the model includes a patientphysiology model based on a physiological pattern and a behavior modelbased on a behavioral pattern.

In Example 13, the subject matter of any one or any combination ofExamples 1-12 may be configured such that the first real-time datumindicates a deviation from an expected behavioral pattern.

In Example 14, the subject matter of any one or any combination ofExamples 1-13 may be configured such that a behavior model indicates atendency to over correct at a meal associated with a meal time, thefirst real-time datum indicates that a mealtime is imminent, and theguidance message corresponds to a lessened overcorrection at themealtime.

In Example 15, the subject matter of any one or any combination ofExamples 1-14 may be configured such that the model includes abehavioral pattern that includes a long-term behavioral pattern based onlong-term patterns of behavior and a short-term behavioral patternassociated with current behavior.

In Example 16, the subject matter of Examples 15 may be configured suchthat the behavior model is based on the long-term behavioral pattern andis further based on the short-term behavioral pattern.

In Example 17, the subject matter of Examples 16 may be configured suchthat the short-term behavioral pattern is based on one or more selectedfrom the group consisting of: engagement with a mobile device,accelerometer data, frequency of checking glucose concentration,calendar data, and any combinations thereof.

In Example 18, the subject matter of any one or any combination ofExamples 1-17 may be configured such that the state is based in part ona measurement model.

In Example 19, the subject matter of Examples 18 may be configured suchthat the measurement model is based on a continuous glucoseconcentration monitoring system associated with the patient.

In Example 20, the subject matter of any one or any combination ofExamples 1-19 may further include measuring glucose concentration datasubsequent to the rendering a guidance message and using the measuredsubsequent data to improve one or more of the models.

In Example 21, the subject matter of any one or any combination ofExamples 1-19 may be configured such that the glucose concentration datameasured subsequent to the rendering is fed back to a measurement modelor the behavior model or the patient physiology model, or to acombination thereof.

In Example 22, the subject matter of any one or any combination ofExamples 1-21 may be configured such that the model includes a patternselected from the group consisting of: a physiological pattern, acontextual pattern, or a behavioral pattern, or a combination of thesepatterns.

In Example 23, the subject matter of any one or any combination ofExamples 1-22 may be configured such that the physiological pattern isbased on a physiology model.

In Example 24, the subject matter of any one or any combination ofExamples 1-23 may be configured such that the model is a based on acombination of patterns selected from the group consisting of: aphysiological pattern, a contextual pattern, or a behavioral pattern.

In Example 25, the subject matter of any one or any combination ofExamples 1-24 may be configured such that the determining a guidancemessage includes determining multiple guidance messages based on thestate and the first real-time datum and selecting one of the determinedmultiple guidance messages further based on the state and the firstreal-time datum.

In Example 26, the subject matter of Examples 25 may be configured suchthat the selecting is further based on a ranking scheme, aprioritization scheme, or based on a comparing of the multiple guidancemessages to one or more associated thresholds.

In Example 27, the subject matter of any one or any combination ofExamples 1-26 may further include determining an expected diabeticresponse of the patient based on the state and the first real-timedatum, and wherein the guidance message is personalized to the patientfurther based on the expected diabetic response, wherein the patient isprovided with an actionable message calculated to move the expecteddiabetic response towards a desired diabetic response.

In Example 28, the subject matter Example 27 may be configured such thatthe desired diabetic response is relative to the state and the firstreal-time datum, and wherein the desired diabetic response is selectedfrom the group consisting of: an improved diabetic response, a potentialimproved diabetic response, an idealized response, or an optimizedresponse.

In Example 29, the subject matter of any one or any combination ofExamples 1-28 may be configured such that the guidance message is basedon a functional relationship between expected diabetic response and adesired diabetic response.

In Example 30, the subject matter of Examples 29 may be configured suchthat the functional relationship is a difference between a glucoseconcentration level associated with the expected diabetic response and aglucose concentration level associated with the desired diabeticresponse.

In Example 31, the subject matter of Examples 30 may be configured suchthat the glucose concentration level associated with the desireddiabetic response is a target glucose concentration level or a targetglucose concentration range.

In Example 32, the subject matter of any one or any combination ofExamples 29-31 may be configured such that the functional relationshipis based on whether the expected diabetic response matches apredetermined condition associated with the desired diabetic response.

In Example 33, the subject matter of Example 32 may be configured suchthat the predetermined condition is a target glucose concentrationlevel, a target glucose concentration range, a glucose concentrationsignal signature, a rate of change associated with a glucoseconcentration level, or a combination thereof.

In Example 34, the subject matter of any one or any combination ofExamples 1-33 may be configured such that the guidance message furthercomprises one or more reasons associated with the functionalrelationship, whereby the patient may be informed as to why the guidancemessage is being rendered.

In Example 35, the subject matter of any one or any combination ofExamples 1-34 may be configured such that the guidance message includesan actionable prompt.

In Example 36, the subject matter of Example 34 may be configured suchthat the guidance message includes an actionable prompt that iscalculated to cause the patient's glucose concentration level to movetowards a target level or a target range.

In Example 37, the subject matter of any one or any combination ofExamples 1-36 may be configured such that the guidance message includesan affirmation of current actions associated with the patient.

In Example 38, the subject matter of any one or any combination ofExamples 1-37 may be configured such that the first real-time datum ismeasured, received, or determined by a smart phone.

In Example 39, the subject matter of any one or any combination ofExamples 1-38 may be configured such that the first real-time datum ismeasured, received, or determined by a wearable device.

In Example 40, the subject matter of any one or any combination ofExamples 1-39 may be configured such that the first real-time datum ismeasured, received, or determined by a wearable device in combinationwith a smart phone.

In Example 41, the subject matter of any one or any combination ofExamples 1-40 may be configured such that the first real-time datum ismeasured, received, or determined by an external device.

In Example 42, the subject matter of Example 41 may be configured suchthat the external device is an accelerometer.

In Example 43, the subject matter of any one or any combination ofExamples 1-42 may be configured such that the first real-time datumincludes a time of day, a characteristic or signature signal measured byan accelerometer, or a location determined by a GPS circuit.

In Example 44, the subject matter of any one or any combination ofExamples 1-43 may be configured such that the first real-time datumincludes a change of state.

In Example 45, the subject matter of any one or any combination ofExamples 1-44 may be configured such that the change of state isdetected by a clock, an accelerometer, or a GPS circuit.

In Example 46, the subject matter of any one or any combination ofExamples 1-45 may be configured such that the first real-time datumincludes a user request for a decision support prompt.

In Example 47, the subject matter of any one or any combination ofExamples 1-46 may be configured such that the first real-time datumincludes data received from a continuous glucose concentrationmonitoring system.

In Example 48, the subject matter of any one or any combination ofExamples 1-47 may further include measuring, determining, or receiving asecond real-time datum, wherein the second real-time datum is used indetermining the state the patient is in.

In Example 49, the subject matter of any one or any combination ofExamples 1-48 may be configured such that the determined personalizedguidance message occurs at a time calculated to be useful in managementof a patient glucose concentration level.

Example 50 is a system comprising: a glucose concentration sensorconfigured to detect a patient glucose concentration level; acommunication circuit configured to receive the patient glucoseconcentration level from the glucose concentration sensor; a memorycircuit including a stored model; and a processor configured to: receivethe patient glucose concentration level; execute stored instructions toapply the patient glucose concentration level to the stored model todetermine a state; and determine a guidance message based at least inpart on the determined state.

In Example 51, the subject matter of Example 50 optionally includeswherein the processor is also configured to determine the guidancemessage based at least in part on a temporal pattern.

In Example 52, the subject matter of any one or more of Examples 50-51optionally includes wherein the model includes a physiologic model,determining a state includes determining a physiologic state.

In Example 53, the subject matter of Example 52 optionally includeswherein the processor is further configured to: determine a behavioralstate; and determine the guidance message based at least in part on thebehavior state.

In Example 54, the subject matter of any one or more of Examples 50-53optionally includes wherein the processor is further configured toprovide a therapy recommendation based at least in part on thedetermined state.

In Example 55, the subject matter of any one or more of Examples 50-54optionally includes wherein the system includes a mobile device, themobile device including the memory circuit, and the processor.

In Example 56, the subject matter of Example 55 optionally includeswherein the mobile device includes the communication circuit, and theglucose concentration sensor includes a glucose concentration sensorcommunication circuit configured to communicate with the communicationcircuit.

In Example 57, the subject matter of Example 56 optionally includeswherein the mobile device communication circuit includes a firstwireless transceiver, and the glucose concentration sensor communicationcircuit includes a second wireless transceiver, wherein the mobiledevice communication circuit and the glucose concentration sensorcommunication circuit communicate using a wireless communicationprotocol.

In Example 58, the subject matter of any one or more of Examples 55-57optionally includes wherein the mobile device includes a user interfaceconfigured to provide guidance message.

In Example 59, the subject matter of Example 58 optionally includeswherein the mobile device is configured to receive user input throughthe user interface, and the processor is configured to receive the userinput and apply both the user input and the patient glucoseconcentration level to the model to determine the state.

In Example 60, the subject matter of any one or more of Examples 55-59optionally includes an insulin delivery system.

In Example 61, the subject matter of Example 60 optionally includeswherein the insulin delivery system includes an insulin pump.

In Example 62, the subject matter of any one or more of Examples 60-61optionally includes wherein the insulin delivery system includes aninsulin pen.

In Example 63, the subject matter of any one or more of Examples 50-62optionally includes a user interface configured to provide the guidancemessage to a patient.

Example 64 is a method of delivering physiologic glucose concentrationmanagement guidance comprising: receiving a datum indicative of aglucose concentration level; determining a state by applying the datumto a model; and determining a guidance message based at least in part onthe state and a temporal pattern.

In Example 65, the subject matter of Example 64 optionally includeswherein the temporal pattern includes a learned pattern of patientbehavior.

In Example 66, the subject matter of any one or more of Examples 64-65optionally includes wherein the temporal pattern includes a calendar.

In Example 67, the subject matter of Example 66 optionally includeswherein determining a guidance message is based at least in part on anupcoming event in the calendar.

In Example 68, the subject matter of Example 67 optionally includeswherein determining a guidance message is based at least in part on aprojected change in insulin sensitivity calculated based at least inpart on the upcoming event in the calendar.

In Example 69, the subject matter of any one or more of Examples 64-68optionally includes wherein the model includes a physiologic model,determining a state includes determining a physiologic state, anddetermining a guidance message includes determining from the temporalpattern and the physiologic model that a transition to an undesirablephysiologic state is likely to occur.

In Example 70, the subject matter of Example 69 optionally includeswherein determining a guidance message includes determining anintervention to avoid the transition to the undesirable physiologicstate and determining, based at least in part on the temporal pattern, atime for delivery of the guidance message to enable intervention toprevent the transition.

In Example 71, the subject matter of any one or more of Examples 64-70optionally includes determining a delivery time for delivery of theguidance message using the temporal pattern.

In Example 72, the subject matter of Example 71 optionally includeswherein determining a delivery time includes selecting a delivery timewhen a host is likely to be available based at least in part on thetemporal pattern.

In Example 73, the subject matter of any one or more of Examples 71-72optionally includes wherein determining a delivery time includesidentifying an upcoming period of patient unavailability and selecting atime for delivery of the guidance message prior to the period of patientunavailability.

In Example 74, the subject matter of any one or more of Examples 64-73optionally includes wherein determining a guidance message includesidentifying a period of patient unavailability based at least in part onthe temporal pattern, and wherein the guidance message is calculated topromote glucose concentration stability during the period ofunavailability.

In Example 75, the subject matter of any one or more of Examples 64-74optionally includes determining an engagement state; determining amessaging frequency based at least in part on the engagement state; anddetermining a time for delivering the guidance message based at least inpart on the messaging frequency.

In Example 76, the subject matter of Example 75 optionally includesdetermining that the engagement state has changed to a changedengagement state; determining a new messaging frequency based at leastin part on the changed engagement state; determining a second guidancemessage; and determining a second time for delivering the secondguidance based at least in part on the new messaging frequency.

In Example 77, the subject matter of any one or more of Examples 64-76optionally includes wherein the state is a disease state describing ahost disease stage.

In Example 78, the subject matter of Example 77 optionally includesreceiving a second datum indicative of a second glucose concentrationlevel; determining a second disease state describing a second hostdisease stage at least in part by applying the second datum to themodel; and determining a second guidance message based at least in parton the second disease state.

In Example 79, the subject matter of any one or more of Examples 64-78optionally includes wherein determining a state includes determining aphysiologic state.

In Example 80, the subject matter of Example 79 optionally includeswherein determining a physiologic state includes determining an insulinstate, an energy absorption state, and an energy expenditure state.

In Example 81, the subject matter of any one or more of Examples 64-80optionally includes receiving a behavioral input, wherein determining astate includes applying both the datum and the behavioral input to themodel.

In Example 82, the subject matter of Example 81 optionally includeswherein receiving a behavioral input includes receiving patient activityinformation.

Example 83 is a method of delivering physiologic glucose concentrationmanagement guidance comprising: receiving a datum indicative of aglucose concentration; determining a physiologic state using the datum;determining a behavioral state; determining a guidance message based atleast in part on the physiologic state and the behavioral state; anddelivering the guidance message using a user interface.

In Example 84, the subject matter of Example 83 optionally includesdetermining a time to deliver guidance that enables timely interventionto affect the glucose concentration.

In Example 85, the subject matter of any one or more of Examples 83-84optionally includes determining a level of interest in guidance based atleast in part on the behavioral state and the physiologic state.

In Example 86, the subject matter of Example 85 optionally includeswherein determining a level of interest in therapy guidance is based atleast in part on prior user requests for guidance.

In Example 87, the subject matter of any one or more of Examples 83-86optionally includes wherein determining a behavioral state includesreceiving a behavioral input and applying the behavioral input to abehavior state model.

In Example 88, the subject matter of any one or more of Examples 83-87optionally includes wherein determining a behavioral state includesconsulting a user calendar of scheduled events.

In Example 89, the subject matter of any one or more of Examples 83-88optionally includes wherein determining a physiologic state includesapplying the datum to a physiology state model.

In Example 90, the subject matter of Example 89 optionally includeswherein the physiology state model includes a glucose concentrationlevel.

In Example 91, the subject matter of Example 90 optionally includeswherein the physiology state model further includes one or more of aninsulin state, an energy absorption state, and an energy expenditurestate.

In Example 92, the subject matter of any one or more of Examples 83-91optionally includes determining a measurement state, the measurementstate including a degree of accuracy or precision of the datumindicative of the glucose concentration.

In Example 93, the subject matter of any one or more of Examples 83-92optionally includes wherein determining a guidance message includesdetermining that a low-probability physiologic state transition islikely to occur, wherein the guidance message provides advance notice ofthe low-probability physiologic state transition.

In Example 94, the subject matter of Example 93 optionally includeswherein the low-probability physiologic state transition includes atransition to low glucose concentration level or a high glucoseconcentration level.

In Example 95, the subject matter of any one or more of Examples 93-94optionally includes wherein determining a guidance message includesdetermining that the low-probability physiologic state transition islikely to occur at a time that is inconvenient, and the guidance messageprovides advance warning of the projected low-probability physiologicstate transition to enable intervention to avoid the low-probabilityphysiologic state transition.

In Example 96, the subject matter of Example 95 optionally includeswherein determining that the low-probability physiologic statetransition is likely to occur at a time that is inconvenient includesapplying a behavior input to a behavioral state model.

In Example 97, the subject matter of any one or more of Examples 83-96optionally includes receiving an additional physiologic parameter,wherein the physiologic state is determined using both the datum and theadditional physiologic parameter.

In Example 98, the subject matter of Example 97 optionally includeswherein the additional physiologic parameter includes a bodytemperature, a heart rate, or a respiration rate.

In Example 99, the subject matter of any one or more of Examples 83-98optionally includes during a learning period, receiving a learning datumdescribing at least one of a physiologic state or the behavioral state,wherein at least one of the physiologic state or the behavioral state isdetermined after the learning period using the learning datum.

Example 100 is a method of determining and rendering a calculatedguidance message personalized and useful to a patient for therapeuticmanagement of their diabetes, comprising: receiving data relating to apatient, the data including a real-time glucose concentration level;determining a patient state by applying the data to a state model; andproviding a therapy recommendation based at least in part on thedetermined state.

In Example 101, the subject matter of Example 100 optionally includeswherein the patient state includes an insulin on board state, an insulinsensitivity state, and a dietary consumption state.

In Example 102, the subject matter of any one or more of Examples100-101 optionally includes wherein the state model is a probabilisticstate model.

In Example 103, the subject matter of Example 102 optionally includeswherein the state model includes state transition probabilities arelearned from retrospective data.

In Example 104, the subject matter of any one or more of Examples100-103 optionally includes refining the state model using data receivedafter delivery of the therapy recommendation.

Example 105 is a method of providing decision support functionality fora user, comprising: loading a model into a memory of a computingenvironment; receiving a datum indicative of a glucose concentrationvalue of the user; and causing a display of a calculated insight on auser interface of the computing environment, the insight calculatedusing at least the model and the datum indicative of the glucoseconcentration value.

In Example 106, the subject matter of Example 105 optionally includeswherein the causing a display is initiated by a user request.

In Example 107, the subject matter of Example 106 optionally includeswherein the user request is associated with data entry of a plannedactivity, and where the calculated insight indicates a user actcalculated by one or more of the models to result in a desired outcomeassociated with the glucose concentration value.

In Example 108, the subject matter of Example 107 optionally includeswherein the desired outcome is a glucose concentration value within apredetermined target range.

In Example 109, the subject matter of any one or more of Examples107-108 optionally includes wherein the desired outcome is a glucoseconcentration value having a rate of change within a predeterminedtarget range.

In Example 110, the subject matter of any one or more of Examples107-109 optionally includes wherein the planned activity is a meal, andwherein the calculated insight is a calculated or predicted effect ofthe meal on the glucose concentration value.

In Example 111, the subject matter of any one or more of Examples107-110 optionally includes wherein the calculated insight displayedincludes an interactive recommendation and at least one factor used indetermining the interactive recommendation.

In Example 112, the subject matter of any one or more of Examples105-111 optionally includes wherein causing a display of the calculatedinsight is initiated by an occurrence of an event that matches apredetermined condition.

In Example 113, the subject matter of any one or more of Examples105-112 optionally includes wherein causing a display of the calculatedinsight is initiated by an occurrence of an event that matches acalculated condition, the calculated condition calculated based at leastin part on the model, or the datum indicative of the glucoseconcentration value, or a combination thereof.

In Example 114, the subject matter of Example 113 optionally includeswherein when a therapy adjustment exposes the user to more risk than waspresent before the therapy adjustment, then adjusting alerts and/oralarms to have additional sensitivity for a period of time following thetherapy adjustment.

In Example 115, the subject matter of any one or more of Examples113-114 optionally includes detecting when a time period existsfollowing a potential treatment decision that triggers a more frequentinstantiation of a CGM app than priori the potential treatment decisionand increasing a messaging frequency of a decision support.

In Example 116, the subject matter of any one or more of Examples113-115 optionally includes wherein the messaging is to the user or to afollower of the user.

In Example 117, the subject matter of any one or more of Examples105-116 optionally includes detecting an occurrence of a trend using thereceived datum, the trend associated with a recognized pattern.

In Example 118, the subject matter of any one or more of Examples105-117 optionally includes receiving a datum from an external datasource.

In Example 119, the subject matter of Example 118 optionally includeswherein the external data source is an insulin pen or pump, and whereinthe calculated insight includes information about insulin on board.

In Example 120, the subject matter of Example 119 optionally includeswherein the external data source is an insulin pen or pump, and whereinthe calculated insight is expressed with two values, one indicating foruse if user exercise is planned, and another indicating for use if nouser exercise is planned.

In Example 121, the subject matter of any one or more of Examples119-120 optionally includes wherein the external data source is anaccelerometer, and wherein the calculated insight includes informationabout an effect of exercise on glucose concentration value.

In Example 122, the subject matter of any one or more of Examples119-121 optionally includes wherein the external data source is a cameraor GPS receiver, and wherein the calculated insight includes informationabout an effect of meal size and composition on glucose concentrationvalue.

In Example 123, the subject matter of any one or more of Examples119-122 optionally includes wherein the external data source is a userinterface, wherein the user interface is configured to received dataabout user goals, and wherein the calculated insight includesinformation about percentage time in a target range and an indication ofthe target range.

In Example 124, the subject matter of any one or more of Examples105-123 optionally includes loading into a memory of a computingenvironment a measurement model of a continuous glucose concentrationmonitoring system associated with the user, and wherein the calculatedinsight is further based on the measurement model.

In Example 125, the subject matter of Example 124 optionally includeswherein the calculated insight is calculated using an algorithm that isbased at least in part on glucose concentration variability orlikelihood and/or severity of glucose concentration excursions.

In Example 126, the subject matter of any one or more of Examples105-125 optionally includes wherein the causing a display is based oncalculations performed on a periodic basis.

In Example 127, the subject matter of Example 126 optionally includeswherein the periodic basis is determined based on of a series ofmealtimes occurring at substantially the same time.

In Example 128, the subject matter of any one or more of Examples126-127 optionally includes wherein the periodic basis is determinedbased on of a series of similar glycemic responses.

In Example 129, the subject matter of Example 128 optionally includeswherein the similar glycemic responses are spikes.

In Example 130, the subject matter of any one or more of Examples126-129 optionally includes wherein the periodic basis is determinedbased on of a series of similar dosing strategies.

In Example 131, the subject matter of any one or more of Examples126-130 optionally includes wherein the periodic basis is determinedbased on basis of a series of unreliable outcomes, where a glucoseconcentration level drifted over a specified percentage or amount awayfrom a target zone following a potential treatment decision.

In Example 132, the subject matter of any one or more of Examples105-131 optionally includes wherein the display of the calculatedinsight includes the display of a probability cone, the probability conebased on prior data of the user.

In Example 133, the subject matter of any one or more of Examples105-132 optionally includes wherein the display of the calculatedinsight includes the display of a probability cone, the probability conebased on population data.

In Example 134, the subject matter of Example 133 optionally includeswherein the population data is culled from persons having one or moredemographic traits in common with the user.

In Example 135, the subject matter of any one or more of Examples105-134 optionally includes wherein the display of the calculatedinsight includes the display of two separate trend indicators, onedetermined using data measured during weekdays and one determined usingdata measured during weekends.

In Example 136, the subject matter of any one or more of Examples105-135 optionally includes wherein the insight is calculated by thecomputing environment.

In Example 137, the subject matter of any one or more of Examples105-136 optionally includes wherein the insight is calculated by aconnected server.

In Example 138, the subject matter of any one or more of Examples105-137 optionally includes wherein the model includes a physiologicmodel and a behavior model.

In Example 139, the subject matter of Example 138 optionally includeswherein the behavior model is configured to determine level of concernfactors, the level of concern factors selected from the group consistingof: concern about physiologic state, consequence of treatment decisions,and/or potential future states.

In Example 140, the subject matter of Example 139 optionally includeswherein the concern about physiologic state is determined by detecting afrequency of checking an application related to diabetes or detectinghow often SMBG values are being entered.

In Example 141, the subject matter of any one or more of Examples139-140 optionally includes wherein the behavior model is configured todetermine level of engagement factors, the level of engagement factorsselected from the group consisting of: response time, level of treatmentactivity, and/or type of support.

In Example 142, the subject matter of any one or more of Examples139-141 optionally includes wherein the computing environment is amobile device, the method further comprising learning the physiologicalmodel by a second computer system, wherein loading the model into amemory of a computing environment includes loading the learnedphysiological model into the mobile device.

In Example 143, the subject matter of Example 142 optionally includeslearning the behavior model by a second computer system, wherein loadingthe model into a memory of a computing environment includes loading thelearned behavior model into the mobile device.

In Example 144, the subject matter of any one or more of Examples142-143 optionally includes wherein the mobile device determines thecalculated insight without requiring access to the second computersystem.

Example 145 is a system comprising: a glucose concentration sensorconfigured to detect a host glucose concentration; a communicationcircuit configured to receive the host glucose concentration from theglucose concentration sensor; a memory circuit including a stored model;and a processor configured to: receive host glucose concentration datasensed by the glucose concentration sensor; determine a host statechange associated with the host glucose concentration data; determine aguidance message based at least in part on the host state change; anddelivering the guidance message through a user interface.

In Example 146, the subject matter of Example 145 optionally includeswherein the processor is further configured to determine that the hoststate change is a typical, wherein the determining of the guidancemessage is based at least in part on the a typicality of the statechange.

In Example 147, the subject matter of any one or more of Examples145-146 optionally includes wherein determining the host state changecomprises determining from a model that a low-probability statetransition has occurred or is likely to occur, wherein the determiningof the guidance message is based at least in part on the determinationthat the low-probability state transition has occurred or is likely tooccur.

In Example 148, the subject matter of any one or more of Examples145-147 optionally includes wherein determining the host state changecomprises identifying a likely transition to an undesirable host stateand the guidance message is determined and delivered at a time such thatthe host can intervene to avoid the transition to the undesirable hoststate.

In Example 149, the subject matter of any one or more of Examples145-148 optionally includes wherein the system includes a mobile device,the mobile device including the memory circuit, and the processor.

In Example 150, the subject matter of Example 149 optionally includeswherein the mobile device includes the communication circuit, and theglucose concentration sensor includes a glucose concentration sensorcommunication circuit configured to communicate with the communicationcircuit.

In Example 151, the subject matter of any one or more of Examples149-150 optionally includes wherein the mobile device communicationcircuit includes a first wireless transceiver, and the glucoseconcentration sensor communication circuit includes a second wirelesstransceiver, wherein the mobile device communication circuit and theglucose concentration sensor communication circuit communicate using awireless communication protocol.

In Example 152, the subject matter of any one or more of Examples145-151 optionally includes an insulin delivery system.

In Example 153, the subject matter of any one or more of Examples145-152 optionally includes wherein the state change is from a firstdisease state describing a first host disease stage to a second diseasestate indicating a second host disease stage, wherein the processor isfurther configured go determine a second guidance message based at leastin part on the second disease stage.

Example 154 is a method of delivering physiologic glucose concentrationmanagement guidance comprising: receiving a datum indicative of aglucose concentration; determining a patient state by applying the datumto a model; determining whether the patient state is a typical;determining a guidance message based on the a typicality of the patientstate; and delivering the guidance message through a user interface.

In Example 155, the subject matter of Example 154 optionally includeswherein determining whether the patient state is a typical includesdetermining whether the patient state is a typical for a given set ofconditions.

In Example 156, the subject matter of any one or more of Examples154-155 optionally includes wherein determining whether the patientstate is a typical includes determining whether a low-likelihood statetransition has occurred.

In Example 157, the subject matter of any one or more of Examples154-156 optionally includes wherein determining a guidance messageincludes determining whether a low-likelihood state transition isprojected to occur.

In Example 158, the subject matter of any one or more of Examples154-157 optionally includes wherein determining a patient state includesdetermining a physiological state and a behavioral state and determiningwhether the physiological state is a typical for the determinedbehavioral state.

In Example 159, the subject matter of any one or more of Examples154-158 optionally includes wherein determining whether the patientstate is a typical includes identifying a blood glucose concentrationlevel that deviates from a controlled blood glucose concentration rangea time or in a circumstance when blood glucose concentration istypically in a controlled range.

In Example 160, the subject matter of any one or more of Examples154-159 optionally includes wherein determining whether the patientstate is a typical includes identifying a blood glucose concentrationtrend leading to a high or low blood glucose concentration state a timeor in a circumstance when blood glucose concentration is typically in acontrolled range.

In Example 161, the subject matter of any one or more of Examples154-160 optionally includes wherein determining whether the patientstate is a typical includes anticipating a shift to a low blood glucoseconcentration state at a time or in a circumstance when blood glucoseconcentration is typically well controlled.

Example 162 is a method of delivering physiologic glucose concentrationmanagement guidance comprising: receiving a datum indicative of aglucose concentration; determining a patient state by applying the datumto a model; determining from the model that a low-probability statetransition has occurred or is likely to occur; and delivering through auser interface a guidance message based on the determination that thelow-probability state transition has occurred or is likely to occur.

In Example 163, the subject matter of Example 162 optionally includeswherein the method includes determining that a low-probability statetransition is likely to occur, wherein the guidance message providesadvance notice of the low-probability state transition.

In Example 164, the subject matter of any one or more of Examples162-163 optionally includes wherein the low-probability physiologicstate transition includes a transition to a low glucose concentrationlevel or a high glucose concentration level.

In Example 165, the subject matter of any one or more of Examples162-164 optionally includes wherein determining a guidance messageincludes determining that the low-probability state transition is likelyto occur at a time that is inconvenient.

In Example 166, the subject matter of Example 165 optionally includeswherein determining that the low-probability state transition is likelyto occur at a time that is inconvenient includes reference to usercalendar of scheduled events.

In Example 167, the subject matter of any one or more of Examples165-166 optionally includes wherein determining that the low-probabilitystate transition is likely to occur at a time that is inconvenientincludes reference to a behavioral state model.

In Example 168, the subject matter of any one or more of Examples162-167 optionally includes wherein delivering the guidance messageincludes determining a time period when the patient or a caregiver islikely to be available to take action to prevent the low-probabilitystate transition and delivering the guidance message during thedetermined time period.

In Example 169, the subject matter of Example 168 optionally includeswherein determining a time period when the patient is likely to beavailable to take action to prevent the low-probability state transitionincludes referencing a calendar of scheduled events.

In Example 170, the subject matter of any one or more of Examples168-169 optionally includes wherein determining a time period when thepatient or a caregiver is likely to be available to take action toprevent the low-probability state transition includes using the model.

In Example 171, the subject matter of any one or more of Examples168-170 optionally includes wherein using the model includes using apattern of user activity or user location information to determine atime period when the patient or a caregiver is likely to be available.

Example 172 is a method of delivering physiologic glucose concentrationmanagement guidance comprising: receiving a datum indicative of aglucose concentration; receiving one or more behavioral, environmentalor contextual inputs; identifying a likely transition to an undesirablepatient state by applying the datum and the one or more behavioral,environmental or contextual input to a model; determining a guidancemessage based on the likely transition to an undesirable patient state;and delivering the guidance message, wherein the guidance message isdetermined and delivered at a time such that the patient can interveneto avoid the transition to an undesirable patient state.

In Example 173, the subject matter of Example 172 optionally includeswherein receiving a behavioral, environmental or contextual inputincludes receiving accelerometer data.

In Example 174, the subject matter of any one or more of Examples172-173 optionally includes wherein receiving a behavioral,environmental or contextual input includes receiving information from acalendar about a scheduled event.

In Example 175, the subject matter of any one or more of Examples172-174 optionally includes wherein receiving a behavioral,environmental or contextual input includes receiving input from a userthrough a user interface.

In Example 176, the subject matter of any one or more of Examples172-175 optionally includes wherein receiving a behavioral,environmental or contextual input includes receiving information from auser about completion, initiation, or anticipation of exercise.

In Example 177, the subject matter of any one or more of Examples172-176 optionally includes wherein receiving a behavioral,environmental or contextual input includes detecting that a user isdriving.

In Example 178, the subject matter of any one or more of Examples172-177 optionally includes wherein receiving one or more behavioral,environmental or contextual input includes receiving locationinformation.

In Example 179, the subject matter of any one or more of Examples172-178 optionally includes wherein receiving one or more behavioral,environmental or contextual input includes receiving an ambienttemperature or an ambient pressure.

In Example 180, the subject matter of any one or more of Examples172-179 optionally includes receiving a body temperature, heart rate, orrespiration rate.

In Example 181, the subject matter of Example 180 optionally includeslearning the model based upon one or more patterns of receivedinformation.

In Example 182, the subject matter of Example 181 optionally includeswherein learning the model includes learning a pattern of insulinsensitivity as a function of time.

In Example 183, the subject matter of Example 182 optionally includeswherein learning the model includes learning a pattern of insulinsensitivity as a function of time elapsed after a period of physicalexertion.

In Example 184, the subject matter of any one or more of Examples172-183 optionally includes determining a user query and providing theuser query to a user, wherein the behavioral, environmental orcontextual input is received in response to the user query.

In Example 185, the subject matter of any one or more of Examples172-184 optionally includes wherein receiving a datum indicative of aglucose concentration includes receiving a datum from a continuousglucose concentration monitoring system.

Example 186 is a system comprising: a glucose concentration sensorconfigured to detect a host glucose concentration; a communicationcircuit configured to receive the host glucose concentration from theglucose concentration sensor; a memory circuit including a stored model;and a processor configured to: accessing a datum associated with a host;determining a state of the host using the datum; determining a guidancemessage based at least in part on the determined state; selecting a timefor providing the guidance message; and providing the guidance messagethrough a user interface at the selected time.

In Example 187, the subject matter of Example 186 optionally includeswherein the time is calculated to enable intervention prior to atransition of the host to an undesirable physiologic state.

In Example 188, the subject matter of any one or more of Examples186-187 optionally includes wherein determining the guidance message isbased at least in part on a personalized behavior model of the host, andwherein the time is calculated to be useful to the host in therapeuticmanagement of diabetes.

In Example 189, the subject matter of any one or more of Examples186-188 optionally includes wherein the determining of the state isbased at least in part on a patient physiology model and a patientbehavioral model.

Example 190 is a method of delivering physiologic glucose concentrationmanagement guidance comprising: measuring, determining, or receiving afirst real-time datum associated with a patient; determining a state thepatient is in using at least in part a model and the first real-timedatum; determining a personalized guidance message, wherein the guidancemessage is based at least in part on the determined state; and providingthe determined personalized guidance message through a user interface ata time calculated to enable intervention prior to a transition to anundesirable physiologic state.

In Example 191, the subject matter of Example 190 optionally includeswherein determining a guidance message is further based on a timing ofthe determining the guidance message or a time associated with thedetermined state.

In Example 192, the subject matter of any one or more of Examples190-191 optionally includes wherein the model includes a stateindicative of a convenience or availability of the patient toparticipate in an intervention.

In Example 193, the subject matter of any one or more of Examples190-192 optionally includes wherein the guidance message is based atleast in part on a projected transition to the undesirable physiologicstate.

In Example 194, the subject matter of Example 193 optionally includeswherein the guidance message is based at least in part on adetermination that a projected transition from a present state to aprojected state is a low-probability transition.

In Example 195, the subject matter of any one or more of Examples190-194 optionally includes wherein the model includes a patientphysiology model, and determining a state the patient is based at leaston applying the first real-time datum to the patient physiology model.

In Example 196, the subject matter of Example 195 optionally includeswherein the model further includes a behavior model.

In Example 197, the subject matter of Example 196 optionally includeswherein the behavior model is based on a machine-learned characteristicof the patient, the machine-learned characteristic based on a behavioralor contextual pattern.

In Example 198, the subject matter of any one or more of Examples196-197 optionally includes wherein the behavior model is based on a setof one or more steps determined to be likely to be performed by thepatient.

In Example 199, the subject matter of any one or more of Examples196-198 optionally includes wherein the behavior model is based on a setof one or more objectives determined to be likely attainable by thepatient.

In Example 200, the subject matter of any one or more of Examples196-199 optionally includes wherein the behavior model is a pattern.

In Example 201, the subject matter of any one or more of Examples196-200 optionally includes wherein the patient physiology model isbased on a physiological pattern and the behavior model is based on abehavioral pattern.

In Example 202, the subject matter of Example 201 optionally includeswherein the first real-time datum indicates a deviation from an expectedbehavioral pattern.

In Example 203, the subject matter of Example 202 optionally includeswherein the behavior model indicates a tendency to over correct at ameal associated with a meal time, the first real-time datum indicatesthat a mealtime is imminent, and the guidance message corresponds to alessened overcorrection at the mealtime.

In Example 204, the subject matter of Example 203 optionally includeswherein the behavioral pattern includes a long-term behavioral patternbased on long-term patterns of behavior and a short-term behavioralpattern associated with current behavior.

In Example 205, the subject matter of Example 204 optionally includeswherein the behavior model is based on the long-term behavioral patternand is further based on the short-term behavioral pattern.

In Example 206, the subject matter of Example 205 optionally includeswherein the short-term behavioral pattern is based on one or moreselected from the group consisting of: engagement with mobile device,accelerometer data, frequency of checking glucose concentration,calendar data, and combinations of these.

In Example 207, the subject matter of any one or more of Examples190-206 optionally includes wherein determining a state is further basedon a measurement model.

In Example 208, the subject matter of Example 207 optionally includeswherein the measurement model is based on a continuous glucoseconcentration monitoring system associated with the patient.

In Example 209, the subject matter of Example 208 optionally includesmeasuring glucose concentration data subsequent to the determining aguidance message and using the measured subsequent data to improve oneor more of the models.

In Example 210, the subject matter of Example 209 optionally includeswherein the glucose concentration data measured subsequent to thedetermining is fed back to a measurement model or the behavior model orthe patient physiology model, or to a combination thereof.

In Example 211, the subject matter of any one or more of Examples190-210 optionally includes wherein the model includes a patternselected from the group consisting of: a physiological pattern, acontextual pattern, or a behavioral pattern, or a combination of thesepatterns.

In Example 212, the subject matter of Example 211 optionally includeswherein the physiological pattern is based on a physiology model.

In Example 213, the subject matter of any one or more of Examples190-212 optionally includes wherein the model is a based on acombination of patterns selected from the group consisting of: aphysiological pattern, a contextual pattern, or a behavioral pattern.

In Example 214, the subject matter of any one or more of Examples190-213 optionally includes wherein the determining a guidance messagefurther comprises determining multiple guidance messages based on thestate and the first real-time datum and selecting one of the determinedmultiple guidance messages further based on the state and the firstreal-time datum.

In Example 215, the subject matter of Example 214 optionally includeswherein the selecting is further based on a ranking scheme, aprioritization scheme, or based on a comparing of the multiple guidancemessages to one or more associated thresholds.

In Example 216, the subject matter of any one or more of Examples190-215 optionally includes determining an expected diabetic response ofthe patient based on the state and the first real-time datum, andwherein the guidance message is personalized to the patient furtherbased on the expected diabetic response, wherein the patient is providedwith an actionable message calculated to move the expected diabeticresponse towards a desired diabetic response.

In Example 217, the subject matter of Example 216 optionally includeswherein the desired diabetic response is relative to the state and thefirst real-time datum, and wherein the desired diabetic response isselected from the group consisting of: an improved diabetic response, apotential improved diabetic response, an idealized response, or anoptimized response.

In Example 218, the subject matter of Example 217 optionally includeswherein the guidance message is based on a functional relationshipbetween the expected diabetic response and a desired diabetic response.

In Example 219, the subject matter of Example 218 optionally includeswherein the functional relationship is a difference between a glucoseconcentration level associated with the expected diabetic response and aglucose concentration level associated with the desired diabeticresponse.

In Example 220, the subject matter of Example 219 optionally includeswherein the glucose concentration level associated with the desireddiabetic response is a target glucose concentration level or a targetglucose concentration range.

In Example 221, the subject matter of Example 220 optionally includeswherein the functional relationship is based on whether the expecteddiabetic response matches a predetermined condition associated with thedesired diabetic response.

In Example 222, the subject matter of Example 221 optionally includeswherein the predetermined condition is a target glucose concentrationlevel, a target glucose concentration range, a glucose concentrationsignal signature, or a rate of change associated with a glucoseconcentration level.

In Example 223, the subject matter of any one or more of Examples217-222 optionally includes wherein the guidance message furthercomprises one or more reasons associated with the functionalrelationship, whereby the patient may be informed as to why the guidancemessage is being rendered.

In Example 224, the subject matter of any one or more of Examples190-223 optionally includes wherein the guidance message includes anactionable prompt.

In Example 225, the subject matter of Example 224 optionally includeswherein the guidance message includes an actionable prompt that iscalculated to cause the patient's glucose concentration level to movetowards a target level or a target range.

In Example 226, the subject matter of any one or more of Examples190-225 optionally includes wherein the guidance message includes anaffirmation of current actions associated with the patient.

In Example 227, the subject matter of any one or more of Examples190-226 optionally includes wherein the first real-time datum ismeasured, received, or determined by a smart phone.

In Example 228, the subject matter of any one or more of Examples190-227 optionally includes wherein the first real-time datum ismeasured, received, or determined by a wearable device.

In Example 229, the subject matter of any one or more of Examples190-228 optionally includes wherein the first real-time datum ismeasured, received, or determined by a wearable device in combinationwith a smart phone.

In Example 230, the subject matter of any one or more of Examples190-229 optionally includes wherein the first real-time datum ismeasured, received, or determined by an external device.

In Example 231, the subject matter of Example 230 optionally includeswherein the external device is an accelerometer.

In Example 232, the subject matter of any one or more of Examples190-231 optionally includes wherein the first real-time datum is a timeof day, a characteristic or signature signal measured by anaccelerometer, or a location determined by a GPS circuit.

In Example 233, the subject matter of any one or more of Examples190-232 optionally includes wherein the first real-time datum is achange of state.

In Example 234, the subject matter of Example 233 optionally includeswherein the change of state is detected by a clock, an accelerometer, ora GPS circuit.

In Example 235, the subject matter of any one or more of Examples190-234 optionally includes wherein the first real-time datum is a userrequest for a decision support prompt.

In Example 236, the subject matter of any one or more of Examples190-235 optionally includes wherein the first real-time datum isreceived from a continuous glucose concentration monitoring system.

In Example 237, the subject matter of any one or more of Examples190-236 optionally includes measuring, determining, or receiving asecond real-time datum, wherein the second real-time datum is used indetermining the state the patient is in.

In Example 238, the subject matter of any one or more of Examples190-237 optionally includes wherein providing the determinedpersonalized guidance message occurs at a time calculated to be usefulin management of a patient glucose concentration level.

In Example 239, the subject matter of any one or more of Examples190-238 optionally includes wherein the state is a disease statedescribing a patient disease stage.

In Example 240, the subject matter of Example 239 optionally includesmeasuring, determining, or receiving a second real-time datum indicativeof a second glucose concentration level; determining a second diseasestate describing a second patient disease stage at least in part byapplying the second datum to the model; and determining a secondguidance message based at least in part on the second disease state.

In Example 241, the subject matter of any one or more of Examples190-240 optionally includes wherein the state is an engagement state,further comprising: determining a messaging frequency based at least inpart on the engagement state; and determining the time for providing thepersonalized guidance message based at least in part on the messagingfrequency.

In Example 242, the subject matter of any one or more of Examples190-241 optionally includes during a learning period, receiving alearning datum, wherein determining the state of the patient based atleast in part on the learning datum.

Example 243 is a method of determining and delivering a calculatedguidance message personalized and useful to a patient in therapeuticmanagement of their diabetes, comprising: learning a personalizedbehavior model of the patient; receiving a real-time datum; determininga personalized guidance message to be rendered to the patient, thedetermining based at least in part on the time of determination of thepersonalized guidance message and the personalized behavior model of thepatient; and determining a delivery time to provide the personalizedguidance message using the learned personalized behavior model, whereinthe delivery time is calculated to be useful to the patient in thetherapeutic management of his or her diabetes.

In Example 244, the subject matter of Example 243 optionally includeswherein learning a personalized behavior model of a patient includesmachine learning a first characteristic of the patient.

In Example 245, the subject matter of Example 244 optionally includeswherein the first characteristic is a pattern selected from the groupconsisting of: a physiological pattern, a contextual pattern, or abehavioral pattern, or a combination of these patterns.

In Example 246, the subject matter of Example 245 optionally includesdelivering the personalized guidance message at the delivery time.

Example 247 is a method of determining and rendering a calculatedguidance message personalized and useful to a patient in the therapeuticmanagement of their diabetes, comprising: measuring, determining, orreceiving a first real-time datum associated with the patient; using amodel, determining a state the patient is in, the determining based on apatient physiology model, a behavioral model, and a measurement model,the state determined by the patient physiology model and the behavioralmodel and the real-time datum; determining a guidance message, whereinthe guidance message is personalized to the patient based on at leastthe determined state, whereby the determined state and use of pluralmodels enables a personalization of the guidance message; and providingthe determined personalized guidance message via a user interface, suchthat the rendering occurs at a time calculated to be useful to thepatient in the therapeutic management of their diabetes.

In Example 248, the subject matter of Example 247 optionally includeswherein receiving a first real-time datum is a glucose concentrationvalue.

In Example 249, the subject matter of Example 248 optionally includeswherein receiving a first real-time datum is a time of day.

In Example 250, the subject matter of any one or more of Examples248-249 optionally includes wherein the patient physiology model is astate model that includes one or more of a glucose concentration state,an insulin-on-board state, and insulin sensitivity state, an energyabsorption state, or an energy exertion state.

In Example 251, the subject matter of any one or more of Examples248-250 optionally includes learning the model from a set of input data.

In Example 252, the subject matter of Example 251 optionally includeswherein the set of input data includes one or more of clock time, timeof day, glucose concentration level, insulin on board, patient activity,patient wellness, day of week, day of month, day of year, location, foodconsumed, or beverage consumed.

In Example 253, the subject matter of any one or more of Examples251-252 optionally includes determining a deviation from an expectedstate after delivering the personalized guidance message, and adaptingthe model based on additional input information.

In Example 254, the subject matter of Example 253 optionally includeswherein the set of input data includes information received through auser interface.

In Example 255, the subject matter of any one or more of Examples247-254 optionally includes wherein providing the determinedpersonalized guidance message includes rendering the personalizedguidance message on a user interface.

This summary is intended to provide an overview of subject matter of thepresent patent application. It is not intended to provide an exclusiveor exhaustive explanation of the disclosure. The detailed description isincluded to provide further information about the present patentapplication. Other aspects of the disclosure will be apparent to personsskilled in the art upon reading and understanding the following detaileddescription and viewing the drawings that form a part thereof, each ofwhich are not to be taken in a limiting sense.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

In the drawings, which are not necessarily drawn to scale, like numeralsmay describe similar components in different views. Like numerals havingdifferent letter suffixes may represent different instances of similarcomponents. The drawings illustrate generally, by way of example, butnot by way of limitation, various embodiments discussed in the presentdocument.

FIG. 1 illustrates an example system for delivering guidance to apatient.

FIG. 2A is an illustration of the model shown in FIG. 1.

FIG. 2B is an illustration that provides a more detailed illustration ofexample model inputs and example states that may be determined byapplying inputs to a model.

FIG. 3A is an illustration of an example timeline associated with apatient.

FIG. 3B is an illustration of an example schedule of a caregiver and achild patient.

FIG. 3C is an illustration of a wake/sleep state of a patient.

FIG. 3D is an illustration of determination of availability (orconvenience) of a patient to participate in an intervention, based onother states.

FIG. 4 is an illustration of various categories of inputs coupled tovarious categories of outputs through a determination step or module

FIGS. 5A, 5B, and FIGS. 6-13 are flowcharts that illustrate examplemethods of determining user guidance.

FIG. 14 is a flowchart illustrating ways of converting non-crisp inputsinto quantifiable criteria.

FIG. 15 illustrates use of one type of correlative parameter within asystem model, e.g., a food sensitivity, in the determination ofdecision-support for a meal bolus.

FIG. 16 illustrates various inputs that may be employed indecision-support application/functionality.

FIG. 17 illustrates various physical sources of input data.

FIGS. 18A and 18B illustrate nontraditional ways of obtaining meal data.

FIG. 19 is a flowchart for obtaining signal signature information whichmay then be employed as an input for decision-support, e.g., for statedefinitions and determination.

FIG. 20 is a chart illustrating gastric emptying duration, which canserve as an input into decision-support, e.g., for state definition anddetermination.

FIG. 21 is a chart illustrating modes, e.g., modes of operation of CGMs,and modes too may be used as inputs into decision-support, e.g., forstate definition and determination.

FIGS. 22A and 22B illustrate user input adjusting threshold levels.

FIG. 23 is an illustration of an example system in which the methodsdiscussed herein may be implemented.

FIG. 24 is a block diagram of an example machine upon which any one ormore of the techniques (e.g., methodologies) discussed herein mayperform.

FIGS. 25A and 25B are illustrations of an example user interface throughwhich a user may select carbohydrate content and fat content on a graph.

FIG. 26 is an illustration of an example user interface through whichalarms may be configured.

FIGS. 27A and 27B are illustrations of a user interface that showspredictive data for selected amounts of carbohydrate ingestion.

FIGS. 28-30 are illustrations of example guidance delivered on a userinterface of a mobile device.

FIGS. 31A and 31B are illustrations of example glucose post-meal trendswithout (FIG. 31A) and with (FIG. 31B) timely decision-support guidance.

FIGS. 32A and 32B are illustrations of example post-meal insulin trenddistribution patterns without (FIG. 32A) and with (FIG. 32B)decision-support guidance.

FIG. 33 is an illustration of example glucose trends involvingintervention to address a hypoglycemic event.

FIGS. 34-37 are illustrations of an example user interface on a device.

FIG. 38 is another illustration of the model shown in FIG. 1.

FIG. 39 is a flowchart showing one example of a process flow that can beexecuted by a decision support system to change in response to changesin the disease stage of the host.

DETAILED DESCRIPTION

Management of diabetes can present complex challenges for patients,clinicians, and caregivers, as a confluence of many factors can impact apatient's glucose level and glucose trends. The present inventors haverecognized, among other things, that intensive insulin users can benefitfrom real-time guidance that is determined or delivered at a time thatis calculated to be useful to a for a patient or caregiver. Thedetermination of timing of such guidance may be supported bytechnological systems that process data and patterns to determinetiming. For example, by employing technical tools such as sensors, datamodels, and patient interface devices, a system may determine a timethat is calculated to be within a time window when the patient orcaregiver is likely to be available to receive and act on the guidance,or otherwise find the guidance useful. In some examples, a system maylearn user preferences or behavioral traits or patterns and use thepreferences, traits or patterns to determine the timing of guidance. Bydelivering guidance at a time calculated to be useful to the user,management of physiologic glucose levels may be improved.

Overview

A system that determines guidance and a time to deliver guidance that iscalculated to be useful to a user (e.g., patient, caregiver, orclinician) may help a user sleep better, for example to getuninterrupted sleep due because glucose levels are controlled, or to goto be with peace of mind and avoid highs and lows while sleeping, orknow what to do to improve sleep by acting on pre-sleep guidance, or toknow when there are potential problems that need to be addressed. Thesystem may alternatively or additionally help a user eat better, forexample by having confidence that a patient can, with guidance from adecision support system, eat and stay in range after eating, or stay inrange through and after a meal regardless of what the patient has doneleading up to a meal, or feel secure knowing that treatment is safe andeffective. The system may alternatively or additionally help a user livebetter (e.g., increase quality of life), for example by knowing when theuser needs to pay attention to diabetes issues (e.g., glucose levels),or to adapt to unexpected events during the day and maintain glucoselevels under control, or to be aware of a potential or likely excursionahead of time to enable time to react, or to respond to an excursionwithout overcorrecting or overeating (e.g., over-consumingcarbohydrates.)

In some examples, delivered guidance may assist patients, caregivers, orhealthcare providers improve lifestyle or clinical/patient outcomes bymeeting a variety of challenges, such as overnight glucose control(e.g., reduce incidence of hypoglycemic events or hyperglycemicexcursions), glucose control during and after meals (e.g. use historicalinformation and trends to increase glycemic control), hyperglycemiacorrections (e.g., increase time in target zone while avoidinghypoglycemic events from over-correctio), hypoglycemia treatments (e.g.,address hypoglycemia while avoiding “rebound” hyperglycemia), exercise,and other health factors. A system may provide therapy optimizationtools that learn a patient's physiology and behavior and calculateguidance to help the patient identify optimal or desirable therapyparameters, such as basal insulin requirements, insulin to carb ratios,correction factors, or changes to insulin sensitivity due to exercise.Decision support tools may, for example, help a patient respond to aproblem in real time by predicting hypoglycemia or hyperglycemia eventsor trends, providing treatment recommendations to address occurring orpotential hypoglycemia or hyperglycemia events or trends, and monitorhow the glycemic, physiologic, or behavioral response in real time. Thistype of calculated guidance and support may relieve the cognitive burdenon the patient, caregiver, or health care professional.

Physiologic sensors such as continuous glucose monitors can provideuseful data that may be used by a patient, caregiver or health careprofessional to manage glucose levels, but the data may requiresignificant processing to develop effective strategies for glucosemanagement. The sheer volume of data, and recognition of correlationsbetween types of data, trends, events, and outcomes, can far exceedhuman capabilities for processing. This is particularly impactful when adecision about therapy or response to a physiologic condition is beingmade in real time. Integration of real-time or recent data withhistorical data and patterns can provide useful guidance in makingreal-time decisions about therapy. Technological tools can process thisinformation to provide decision support guidance calculated to be usefulfor a particular patient in a particular condition or situation at aparticular time. Technological tools may also reduce the cognitiveburden on human decision-makers by repetitively making calculationsthroughout the day and determining when guidance is to be delayed ordelivered.

A decision-support system may be particularly useful in developingpre-sleep guidance to increase the likelihood that glucose levels arecontrolled during sleep. For example, a system may use an algorithm ormodel to determine whether a hyperglycemia or hypoglycemia event ispossible or likely and develop guidance, which may for example include apre-sleep action item such as insulin delivery, eating a food item(e.g., fast carbs, slow carbs, or carbs in combination with protein), orsetting an alarm to check a status or check for guidance at a particulartime. A system may also use an algorithm or model to provide contextsensitive alerts. For example, a system may be aware from human input orsensor input or behavioral patterns that a user is sleeping or about tosleep and take the sleep activity into account in calculating an alertor a time to deliver an alert. In some examples, a system may delaydelivery of an alert or guidance (e.g., until a risk condition issatisfied or intervention time window opens) to avoid unnecessarilywaking a patient or caregiver. In some examples, a system may calculatea time to deliver guidance (and an alert that may wake a patient or timegiver) to increase the likelihood that a less disruptive intervention isavailable. For example, the system may determine that an inquiry isdesired (e.g., check for compression low, or check of fever or bloodglucose or other physiologic sensor) or a basal or bolus adjustment isneeded, for example to avoid a hyperglycemic event with timely deliveryof insulin via injection or pump, or avoid a hypoglycemic event byreducing insulin deliver via a pump to avoid later waking the patient todeliver carbohydrates through food or drink.

A decision support system configured to calculate guidance and timing ofguidance may also assist with transitions to new therapies or newenvironments or progressions of the disease over time (e.g. changes inpancreatic function or fading of a “honeymoon” period of partialfunctioning of the pancreas, changes in treatment routines for Type IIdiabetics, etc.), for example by providing guidance about potentialoutcomes, notifications about when a decision may be required, orguidance about the potential impact of therapeutic interventions orbehavioral decisions (e.g., exercise, rest, or eating.)

A decision support system may use a variety of sources of information todetermine guidance, such as patterns or other information relating toeating behavior (e.g., number of meals per day, meal size distributionacross meals and snacks, size of treatments for hypoglycemic excursions,or the number of repeat treatments for a hypoglycemic event), insulindose information (e.g., bolus and basal dose patterns, pump settings orinjection patterns, number of boluses per day, amount of trendadjustment, pre-meal bolus patterns, behavior around correction boluses,number of correction boluses per day, behavior patterns (presence andaccuracy of carb-counting, incidence of action or inaction in responseto hyperglycemia or need for a correction bolus, conditions, thresholdsor triggers for corrections (e.g., glucose level, combination of trendand level, food or other factors), awareness of insulin on board, timingof insulin, “pre-bolus” patterns before meals and duration thereof,errors in insulin delivery or therapeutic intervention, exercise timing,exercise duration, and exercise intensity, physiological response toactivity), physiological factors (patterns in response to insulin orcarbohydrates or other foods, tendency to “rebound” to a hyperglycemicstate after a low glucose, impact of illness or medication on insulinsensitivity or glucose levels), responsiveness to guidance (time toacknowledge alert or alarm, behavior in response to alert or alarm(e.g., eating or sleeping or exercise), and glycemic outcomes (e.g.,percentage of time below one or more glucose concentration thresholds(e.g., below 70 mg/dL, below 50 mg/dL), percentage of time above one ormore glucose concentrations threshold (e.g. above 180 mg/DL, above 250mg/DL), and number of events below or above one or more thresholds,)disease stage and/or treatment type (e.g., Type I honeymoon period, TypeII prediabetic stage, Type II oral medication stage, Type II basalinsulin stage), etc. Additional example inputs are described below.

A decision-support system may communicate or interact with othersystems, such as glucose delivery devices (e.g., pumps or smart pens)and other analytical systems.

Exemplary embodiments disclosed herein relate to the use of a glucosesensor that measures a concentration of glucose or a substanceindicative of the concentration or presence of another analyte. In someembodiments, the glucose sensor is a continuous device, for example asubcutaneous, transdermal, transcutaneous, non-invasive, intraocularand/or intravascular (e.g., intravenous) device. In some embodiments,the device can analyze a plurality of intermittent blood samples. Theglucose sensor can use any method of glucose measurement, includingenzymatic, chemical, physical, electrochemical, optical, optochemical,fluorescence-based, spectrophotometric, spectroscopic (e.g., opticalabsorption spectroscopy, Raman spectroscopy, etc.), polarimetric,calorimetric, iontophoretic, radiometric, and the like.

The glucose sensor can use any known detection method, includinginvasive, minimally invasive, and non-invasive sensing techniques, toprovide a data stream indicative of the concentration of the analyte ina host. The data stream is typically a raw data signal that is used toprovide a useful value of the analyte to a user, such as a patient orhealth care professional (HCP, e.g., doctor, physician, nurse,caregiver), who may be using the sensor.

Although much of the description and examples are drawn to a glucosesensor capable of measuring the concentration of glucose in a host, thesystems and methods of embodiments can be applied to any measurableanalyte. Some exemplary embodiments described below utilize animplantable glucose sensor. However, it should be understood that thedevices and methods described herein can be applied to any devicecapable of detecting a concentration of analyte and providing an outputsignal that represents the concentration of the analyte.

In some embodiments, the analyte sensor is an implantable glucosesensor, such as described with reference to U.S. Pat. No. 6,001,067 andU.S. Patent Publication No. US-2011-0027127-A1. In some embodiments, theanalyte sensor is a transcutaneous glucose sensor, such as describedwith reference to U.S. Patent Publication No. US-2006-0020187-A1. In yetother embodiments, the analyte sensor is a dual electrode analytesensor, such as described with reference to U.S. Patent Publication No.US-2009-0137887-A1. In still other embodiments, the sensor is configuredto be implanted in a host vessel or extracorporeally, such as isdescribed in U.S. Patent Publication No. US-2007-0027385-A1. Thesepatents and publications are incorporated herein by reference in theirentirety.

Systems and methods for decision support using lifestyle factors aredescribed in U.S. patent application Ser. No. 15/417,008, entitled“System And Method For Decision Support Using Lifestyle Factors”, whichclaims benefit of U.S. Provisional Patent Application Ser. No.62/289,825, filed Feb. 1, 2016, both of which are incorporated herein byreference in their entireties.

General Description of an Example System

Delivering of guidance at a time or in circumstances that promote timelyaction upon of such guidance may promote effective diabetes managementand reduce the burden of managing blood sugar levels. This may be due atleast in part to the relevance of the guidance, or the availability orinterest of the patient or caregiver to receive and act upon it. Invarious examples, real-time data, models or other pattern information,patient input, and other sensors and sources of user-specificinformation may be used to determine a time to determine and deliverguidance.

An example decision-support system may consider data from include avariety of data sources, such as physiologic sensors, historicalinformation, and other information about the patient or caregiver todetermine a guidance time calculated to be useful to a user such as apatient or caregiver. The time may be calculated, for example, based ontiming factors or patterns, or based upon the occurrence ofcircumstances, which may be recognized from earlier-observed patterns.The circumstances may, for example, be physiologic,behavioral/contextual, or both. In some examples, referencing knownpatterns and associated glucose control tendencies, the determining ortiming of guidance may be calculated to be useful to a user, in view ofthe reoccurrence of circumstances similar to the known pattern.

In some examples, an example real-time decision support system andmethod may provide guidance to a patient in real-time, i.e. at a timethat enables the patient to intervene in their glucose management toavoid an undesirable glucose level or trend, and at a time that iscalculated to be useful to the patient. The timing of delivery of suchreal-time guidance may be determined, for example, using informationfrom a calendar, physiologic sensors, or contextual sensors such as GPSor wireless connections, so that the guidance may be is delivered at atime calculated to make real-time intervention possible or convenientfor the user.

An example real-time decision support system may include a source ofreal-time information about a patient, such as a continuous glucosemonitor (“CGM”, further described below). A continuous glucose monitormay provide information about a glucose level of a patient (“CGM data”)at periodic intervals, such as once a minute or once every five minutes,or upon request. The information may be pushed out by the CGM, or may bepulled by an external device, e.g. by a smart phone or other hand-helddevice that is held or swept over a sensor.

An example real-time decision support system may also include aprocessing system that receives CGM data and other information such asinsulin delivery, caloric consumption, activity, wellness or sicknessstatus, and other sensed or user-entered information about the status,environment, behavior, or wellness of the patient. CGM data and otherdata may be combined and processed to develop guidance for delivery tothe patient. The guidance may be developed based upon timing factors,such as timing of insulin delivery, calorie consumption, type ofcalories consumed, information about absorption or digestion times forfood or beverage types or quantities or combinations, exercise timingand post-exercise oxygen or calorie consumption, and patientavailability or convenience to participate in intervention, such asinsulin delivery or delivery change or exercise or a dietary change.

Models

In some examples, a model may be constructed to process CGM data andother information. The model may, for example, be a state model. One ormore states may be determined by applying one or more inputs to themodel. States may be predefined, or may be learned from analysis ofdata, or both. In some examples, decision support system may be drivenby combining the output of at least two models: (1) a physiologicalstate model, and (2) a behavioral or contextual model. In some examples,decision support may be driven by at least three models, e.g. 1) by aphysiological model and separate behavior and context models, or 2) by aphysiologic, a behavioral/context model, and a measurement model(further described below). Other variants with larger numbers of modelsand sub-models are also possible.

Physiologic Model

In some examples, a physiologic state of the patient may be determinedby applying one or more inputs to a physiologic model. One or morephysiologic states may be used to determine patient guidance, the timingof guidance, or both. For example, one or more inputs (which aredescribed in detail below, e.g. see FIG. 2B, and 14-16 and descriptionthereof), may be applied to a model, or a plurality of models, todetermine a physiologic state that a patient is in. The physiologicstate may, for example, include as a glucose concentration level (e.g.blood glucose level or glucose concentration in other body fluids suchas interstitial fluid), a falling or rising glucose concentration level(i.e., glucose trend), or a rate (e.g. slope or higher-level derivative)of a falling or rising glucose concentration level. A determinedphysiologic state may also be or include activity level (e.g. exercisedetected from an accelerometer, heart rate sensor, or respirationsensor), metabolic drive (e.g. glucose consumption rate), and insulinresistance (e.g. in response to stress hormone secretion, sickness, orhigh blood sugar levels), insulin sensitivity (discussed in greaterdetail below), insulin on board, insulin time to action, insulin actiontime, carb to insulin ratio. Other physiologic states are possible.

Behavioral or Contextual Models

Behavioral or contextual models may be related and may in some examplesbe combined into a single model. A behavioral model may relate todecisions of a user, whereas a contextual model may relate to a user'senvironment (e.g., a location). In some examples a behavioral model mayinclude contextual aspects (e.g., location may be considered a subset ofbehavior, as a user's location is typically a result of a user'schoice). In other examples, two separate models may be provided toaccount for behavioral and contextual factors.

In some examples, a behavioral or contextual state may be determined byapplying inputs to a behavioral model. The behavior or contextual statemay be used to determine guidance, the timing of guidance, or both. Abehavioral or contextual state (e.g. unavailable, or worried abouthypoglycemia) may be determined by applying inputs to the behavioral orcontextual model. The inputs to the behavior model may include adetermined physiologic state. Other inputs to a behavioral or contextualmodel may include user-provided input, real-time parameters (e.g., clockvalues), measurement data or sensed data, calendar information, storedpattern information (e.g. inputs or states correlated to time), oroutputs from other models. User-provided input to a behavioral orcontextual can include, in some examples, an indication of the host'scourse of treatment and/or disease stage. Additional inputs aredescribed below and illustrated in FIGS. 2B and 14-16. In some examples,a behavioral model may include contextual aspects. In another example,the contextual aspects may form another model.

Measurement Model

A measurement model may at least in part assess or confirm thereliability of one or more measurement inputs, such as CGM data orinformation from a CGM model, blood glucose meter data (e.g. from afinger-prick sensor) received via a user interface or from a smart meter(e.g., configured with communication capability to send or transmitvalues), measured blood glucose dosing information (e.g. dosageinformation received from an insulin “smart” pen configured to track andcommunicate dosing information), insulin dosing information receivedfrom a pump, or insulin data entered by a user via a user interface(e.g. volume of insulin injected via needle or pump). A measurementstate obtained from the measurement mode may be provided as input toanother model.

Determination of Guidance and Timing

A decision support engine may determine guidance for a user (patient orcaregiver such as parent or clinician) and a timing for determination ordelivery of the guidance, based at least in part on one or more modelstates, and may provide guidance to a user via a user interface, such asthrough a mobile device. The decision support engine may provide“real-time” guidance based on recent information (e.g., recent CGM data)that the user may use to affect a blood glucose level trend (e.g. averta high or low glucose concentration trend or level.)

Use of Machine Learning to Determine States and Guidance

In some examples, a machine learning method may be used a-priori toidentify possible states. In other words, a universe of possible statesmay be deduced from a set of data. For example, a “post-activity state”may be identified as a state of increased insulin sensitivity up to acertain period of time (e.g., 8 hours) after exercising. Then in realtime, the system may use real-time exercise data (e.g., activity data,heart rate, or respiration) to see that the user is entering such astate, and thus provide guidance that the user take less insulin thanusual, due to the increased insulin sensitivity. Machine learning mayalso be used to identify sets of input variables that lead to aconsistent insulin sensitivity model that can be applied when in thatstate. In another example, machine learning techniques may be used todetermine that a patient always ignores alerts during certain times ofday (e.g. the hours of 3-5 PM), and thus the system may turn offnon-essential alerts during those times, and trigger a risk report asguidance right before the period of time (e.g. shortly before 3 PM), ordeliver advance alerts to the user to prepare the user for the period oftime in which alerts tend to be ignored.

Example System

FIG. 1 shows an example system 100 for determining guidance and timingof guidance using sensor input and a model. The system may processphysiologic inputs, e.g., inputs relating to management of glucoseconcentration levels, to determine a time that is calculated to beuseful to the patient or other user for determination or delivery ofguidance.

The system 100 may include a decision support engine 104 that mayprocess information about a patient (e.g., received real-time sensordata) and combine the sensor information with patterns, e.g. temporal,physiological, or behavioral patterns, or combinations thereof, toproduce outputs that may be provided as guidance, or processed todevelop guidance. The decision support engine 104 may produce a varietyof outputs, which may be provided to the patient 102 as guidance via auser interface 108, or may be used to determine guidance, or may be usedto determine the timing of guidance. The guidance may, for example,include diabetes therapy guidance.

Example Inputs Example Implementations of the Decision Support Engine

One or more sensors 106 may be associated with the patient to provideinformation about the patient to the decision support engine 104. Thesensor 106 may, for example, include an analyte sensor such as a glucosesensor as described above. The sensor 106 may be a transdermal sensor, abody fluid sensor such as a contact lens sensor or dermal sensor, or animplantable sensor configured to measure qualities of interstitial fluidor blood. For example, the sensor 106 may be a subcutaneous,transdermal, transcutaneous, non-invasive, intraocular and/orintravascular glucose sensor, as described above. In some examples, thesensor may be a wearable or implantable sensor that is connected to thepatient 102, such as a continuous glucose monitor sensor available fromDexcom™, Abbot™ (e.g., the Libre™ sensor), or Medtronic™ (e.g. theEnlite™ sensor). Other types of sensors may also be associated with thepatient, such as a heart rate sensor, respiration sensor, other types ofanalyte sensors, motion sensor (e.g. accelerometer), posture sensor(e.g. 3-axis accelerometer), or acoustic sensor (e.g. to capture ambientsound or sounds inside the body). Sensor 106 may be wearable, e.g. on awatch, glasses, contact lens, patch wristband, ankleband, or otherwearable item, or may be incorporated into a handheld device (e.g., asmartphone), or may be incorporated into another sensor, such as acontinuous glucose monitor sensor. In some examples, the sensor 106 mayinclude a multi-sensor patch that may, for example, detect glucoselevels, heart rate, respiration (e.g., using impedance), activity (e.g.using an accelerometer), posture (e.g. using an accelerometer), galvanicskin response, tissue fluid levels (e.g. using impedance or pressure).In some examples, an array or network of sensors may be associated withthe patient. The one or more sensors 106 may communicate via wired orwireless (e.g., Bluetooth, Zigbee, Z-Wave, NFC) communication with alocal device 108, which may, for example, be a mobile device such as asmartphone. A system may learn the joint distribution of signals fromvaried sensors (e.g. from sensors on a multi-sensor patch, or fromnetworked sensors or a group of sensors. The system may use thehistorical data or knowledge of the joint distribution of signal (e.g.,how sensor signals relate to one another or move together) to A)determine or impute (e.g. using a model, algorithm or calculation, asfurther described below) missing sensor data points, or B) to predictfuture blood glucose concentration levels, or C) to detect sensorfailures or problems with performance of a CGM sensor based on jointsignals recorded in real time and historical information, or D) toestimate the number of carbohydrates, fat, protein or other substanceingested based on sensor information, or any combination thereof.

The decision support engine 104 may receive sensed information 120. Thesensed information 120 may, for example, include physiologic data suchas CGM data from a CGM sensor, activity data (e.g. from anaccelerometer), heart rate, or any of the other physiologic describedherein. The sensed information may be sensed by the one or more sensors106, the local device 108, or other sensor device. The sensedinformation may also non-physiologic data, such as location information(e.g. GPS) or connectivity information (e.g. Wi-Fi).

Input to the decision support engine 104 may also include insulin data122. Insulin data may, for example, be captured from an insulin deliverydevice such as a pump or may be received from a smart pen that isconfigured to track insulin delivery and communicate insulin deliveryinformation to the system, e.g. via wireless communication to a smartdevice that may relay the information to the decision support engine.Insulin data may also be received from a user, e.g. from a patient orcaregiver through a user interface on a smartphone or other computerdevice.

The decision support engine 104 may also receive other information 124,such as meal information, sleep information, or calendar information,which may include sensed information (e.g. sleep detected using anaccelerometer or physiologic sensor), learned information (e.g. temporalpatterns), or information supplied from a user via a user interface(e.g. meal or schedule information. Additional inputs that may bereceived by the decision support engine 104 are described in referenceto FIGS. 2A, 2B, and 14-16. Addition details on example systemcomponents are described in reference to FIGS. 23-24. Meal orcarbohydrate information may be received via a user interface on adevice (e.g. smart mobile device) that is paired with a CGM or may bereceive from a different application or different device (e.g.,carbohydrate information may be pulled from a health app or an app ordevice associated with a pump.)

Example Implementations of the Decision Support Engine

The decision support engine may include one or more models 110. The oneor more models 110 may, for example, include a state model. In anexample, a “virtual patient” model may include known information aboutthe patient, which may be based on a template model formed from knownfactors or derived from population data, or may be learned frominformation about the patient, or a combination thereof. The model may,for example, reflect physiological information and behavioralinformation. Physiological information may include, for example, factorssuch as glucose or insulin sensitivity, response to physical activity orstress, illness, fatigue or rest, growth rate (e.g. in children), orbasal metabolism. Behavioral information may include, for example,factors such as ingestion of food or drink, exercise, administration ofinsulin, schedule, e.g. as described by calendar appointments, interestin guidance. In a state model, factors such as these may be representedas states, which may be discrete (e.g., high, medium, low) or continuous(e.g., determined by a function). The one or more models 110 may includea pattern, which may, for example, include a physiological pattern, acontextual pattern, or a behavioral pattern, or a combination of thesepatterns. A physiological pattern may, for example, be based on aphysiology model.

In some examples, two or more models may work together to determineguidance. For example, a physiological model 112 and a behavioral model114 may interact to determine glucose management guidance that accountsfor both the patient's physiology and the patient's behavior. In someexamples, the output of one model may be an input to the other model. Invarious configurations, the models 112, 114 may be independent, or themodels may be sub-models of the model virtual patient model 110. In someexamples, the models may also interact with a measurement model 116,which may for example be a continuation glucose monitoring model. Themeasurement model may include factors such as sensor accuracy,calibration factors, time since insertion, time since calibration (forsystems that use calibration), sensor status (e.g. failed sensor orsensor presence), or communication status (e.g. signal loss).

In various examples, the decision support engine 104 may reside on aremote resource 109, a local device 108, or a combination thereof (e.g.a “hybrid configuration”). The decision support engine 104 may reside onor be connected to one or more remote resources 109 (e.g. cloud servers)by a network, such as a cellular network, Wi-Fi network, the internet,or combinations thereof. The cloud servers 109 may collect and storeinformation received from sensor 106. The cloud servers may also collectother information, such as user calendar information, e.g. informationreceived from a calendar of a patient or patient caregiver. In someexamples, the decision support engine 104 may reside on a device nearthe patient, e.g. the local device 118. In some examples, the decisionsupport engine 104 may reside on a local device but receive assistanceor periodic updates from a remote system. In a hybrid configurationexample, the decision support engine 104 may be distributed between thelocal device 118 and a remote system, e.g. initial processing may beconducted on a local device (e.g., smartphone), with more complexprocessing requests routed to a remote resource that may have higherprocessing power. A hybrid configuration may maintain or improve theperformance of the local device 108, by avoiding overloading the localdevice with excessively complex processing tasks. A hybrid configurationmay also improve the performance of the system, as some tasks may beperformed quickly and without network access by the local device 108,yet more complex tasks may still be possible by leveraging the largerprocessing power of a remote resource 109.

As a practical matter, it may also be desirable to avoid overloadingremote resource 109 with requests from a multiplicity of patients. In anexample, the local device may send data to the remote resource 109periodically (e.g., in real time or on a schedule or when a connectionis available, or any combination thereof), and the remote resource mayperiodically assess the data for a particular user, such as once perhour or once per day. The remote resource 109 may, for example, examinethe received data, or a data set augmented with or containing thereceived data, to look for problems or potential insights. The remoteresource 109 may, for example, update a model to reflect or account forthe new data. In various examples, the remote resource may send anupdate (e.g., pushed by the remote resource 109 or as requested by thelocal device 108) to the local device to address a problem, insight, ormodel update learned from the new data or augmented data set.

Example Determination of Timing of Guidance by the Decision SupportEngine

The decision support engine may process the various inputs, e.g. applythe inputs to one or more models, and determine a time for guidance thatis calculated to be useful to the user. In various examples, the timingof guidance may be calculated to enable a user to improve a user's sleepexperience, eating experience, or quality of life. For example, thesystem may identify a potentially problematic pattern, and determine atime to deliver guidance, where the guidance delivery time is calculatedto avoid interrupting sleep, or to maintain blood glucose control whileproviding the user with flexibility in meal selection or timing, or toprovide sufficient advance-notice of a potential problem (e.g.,high-glucose excursion or low-glucose level) so that a user can adapttheir behavior or react to the problem in a timely manner.

In an example, the system may promote healthy or uninterrupted sleep bydetermining that a problem is likely to occur at a time when a user islikely to be sleeping (e.g., 2 AM) and calculating a time to deliverguidance when the user is likely to be available (e.g., 9 PM). Thesystem may recommend an action, such as eating a pre-sleep snack toavoid a night-time low, to avoid the need to wake the user during thenight. In an example, the system may receive a glucose value anddetermine, based on a learned model of the patient, that the patientwill likely have a hypoglycemic event when the user (caregiver orpatient) is likely to be sleeping, and determine guidance and a time todeliver the guidance to avoid interrupting sleep of a patient orcaregiver.

In another example, the system may determine a pattern in nighttimeblood glucose concentrations levels or trends and delivery guidance tochange a behavior or therapy. For example, the system may recommend abasal dose increase if the system detects a pattern of glucose levelsrising through the night so that the glucose concentration level ortrend satisfies a condition (e.g., over a specified value (e.g. 130mg/DL or a change over a specified amount (e.g. more than 30 or morethan 40 mg/dL increase during sleep or during a specified periodassociated with sleep (e.g. 12-5 AM)). In another example the system mayrecommend a basal dose decrease when the system detects a pattern ofglucose concentration level decreasing a specified amount or rateotherwise satisfied a condition.

In another example, the system may support meal-time decisions bydelivering guidance calculated to be useful in maintaining blood glucosecontrol while providing a user with a flexibility in decisions aboutwhat and when to eat. In an example, the system may determine that aglucose level is likely to trend high before a meal time and determine atime to deliver guidance about a correction bolus before the meal toavoid a need to delay eating when the meal time arrives. For example,the system determine that a user should “pre-bolus” a specified amountof time before a meal (e.g., deliver insulin 20 minutes beforecommencing eating), and the system may determine a time to deliver theguidance to deliver the bolus so that a meal can begin at a plannedtime, or a time that aligns with a learned pattern. In some examples,the length of the pre-bolus window (amount of time between delivering aninsulin bolus and commencing eating) may be determined by the system,and the timing of guidance may be calculated to afford the user time toaccommodate the calculated pre-bolus window. For example, the system maydetermine that a 30-minute pre-bolus is needed to affect a high glucoselevel before a patient eats the next meal. In an example, the system maydeliver guidance 30 minutes before a scheduled meal to prompt a user todeliver the pre-bolus. In another example, the system may provideadditional time for the user accommodate the pre-bolus, e.g. the systemmay determine that pre-bolus guidance be delivered 60 minutes before ameal to allow the user 30 minutes advance notice of the need to delivera pre-bolus 30 minutes prior to eating.

In another meal-time example, the system may calculate a time to deliverguidance during or after a meal. For example, the system may determinethat insulin is rising faster than normal and may determine thatguidance should be given to deliver an additional dose of insulin. In anexample, the system may calculate a time to deliver guidance to optimizeglucose control. For example, the system may determine that guidanceshould be given during a meal to deliver additional insulin. In anotherexample, the system may calculate a time to deliver guidance so as toavoid interrupting a meal. This may be accomplished, for example, byreference to a user calendar, or based upon a pattern of behavior (e.g.,average meal time), by use of a physiologic sensor (e.g., an activitysensor), or through use of location information (e.g., detecting that auser has left a restaurant.)

In some examples, the system may be designed to improve a patient orcaregiver's quality of life by calculating a time to deliver guidance toprovide sufficient advance-notice of a potential problem (e.g.,high-glucose excursion or low-glucose level) so that a user can adapttheir behavior or react to the problem in a timely manner. For example,the system may determine that an excursion (e.g., high-glucose trend) islikely to occur and determine a time to deliver guidance that allows theuser to deliver take corrective action (e.g., deliver a correctionbolus, or exercise) to counter-act the likely excursion. In someexamples, the system may calculate and/or predictable times to deliverguidance, to enable a user to focus on other activities and anticipatedelivery of guidance. For example, the system may deliver guidance everytwo hours during the day. In some examples, the system may determine arecurrent schedule to delivery guidance. In some examples, the systemmay deliver guidance regarding the need for a user's attentiveness toglucose management. For example, the system may calculate a probabilityof the need for user intervention (e.g., determine the risk of a bloodglucose concentration level moving out of a specified range), and notifythe user when a condition is satisfied (e.g., when the probabilityexceeds a threshold). In some examples, the system may periodicallynotify the user that no intervention is required (e.g., “Lookinggood:Glucose levels are well controlled”.)

In some examples, the system may deliver guidance about when to checkthe system for further guidance. For example, the system may receivemeal information, such as meal content and an anticipated or actual(present or past) meal time and advise the user to check back forfurther guidance in a specified amount of time, e.g. “Check back forfurther guidance in 30 minutes.” In another example, the system maydeliver pre-sleep guidance, and ask the user to check back after apre-sleep activity has been completed, e.g. “Eat a small snack and checkback 10 minutes after eating.”

In some examples, the timing of guidance may be calculated based in parton user-defined preferences, such as a preference about whether the userwants to be interrupted during a meal, or the conditions under which theuser want to be interrupted, or time periods during which the userprefers to be interrupted or prefers not to be interrupted.

In some examples, the timing of guidance may be provided related to acurrent user activity based upon real-time data and patterns learnedfrom past activity. For example, to determine a useful time to deliverguidance, the system may integrate real time physiologic data (e.g. CGMdatum) with known physiologic and behavioral patterns (e.g., a model) todetermine both the nature of the guidance, and the timing of theguidance. The system may, for example, learn a glucose response after aparticular meal. When real-time data suggests that the user is going toeat the same meal, or a similar one (e.g., as determined from GPSinformation or Wi-Fi connection to a restaurant), an insight may bedelivered based on the pattern learned from past activity. In otherexample, real-time data may suggest that a user is going to bed, or hasa meeting coming up, and such data may be used to determine a time todeliver guidance, e.g. the real-time information may indicate thatdecision-support should be given soon, or sooner than it would otherwisebe given, to avoid interrupting an upcoming activity (e.g., sleep or ameeting.)

In some examples, the timing of determination of guidance may balancethe need for data to determine a state with the need for timely actionand a need to avoid unnecessary or excessive interruptions to thepatient. Generally, as more time passes, more data is available to useto obtain a curve fit against a pattern or to apply against a model,which may drive more accurate conclusions about states, probabilities,or the appropriate guidance. For example, four hours after eating, mostof the data regarding the body's response to a meal is known. But afterone hour, while the full response is not yet known, it is generallydiscernable approximately how much the user ate, or whether the insulindelivered is appropriate for the consumed meal. After two and a halfhours, these determinations can be made with even more accuracy. In somecases, the user may administer a correction bolus, or the user may betold to eat more, e.g., because the patient did not consume as much asthey thought they did, and they may now be in danger of trending to lowglucose levels. This additional information about food intake or insulinadministration may also be processed by the system. In this example, atiming for delivering of guidance may be determined based on informationthat becomes available after eating. This may include one or more of thefood consumption information, insulin information, glucose levelinformation, other physiology information (e.g. activity), and knownphysiologic patterns (e.g., from a physiology model). Timing may also bebased upon user preferences (e.g., preferences about the frequency ortiming of alerts, e.g. alert often/less often or alert early/late oralert according to a prescribed or learned schedule), which may belearned from data (e.g., as states) or entered as user input.

Returning to the post-meal example described above, somewhere betweenthe time that the user eats the meal and the time an alert is triggered,it may be determined when to trigger an alert. This determination maytake into the fact that if the alert is delayed, e.g. the system waitsto determine guidance or delivery of guidance, the guidance, orunderlying states from which guidance may be determined, will likelyincrease in accuracy as time passes. But if the system waits too long,an optimal or desired window of opportunity for delivering guidance andadministering therapy may have passed, e.g., an undesirable glucosetrend or insulin sensitivity level may develop while the system waitsfor data to accumulate: When glucose levels rise beyond a normal range,a patient's body tends to become insulin resistant, which may make itmore difficult to return the glucose levels to a normal range usinginsulin, and thus may require a larger dose of insulin. The larger doseof insulin may increase the risk of the patient trending to low glucoselevels when the insulin resistance (and high glucose level) iseventually overcome. On the other hand, when glucose levels trend toolow, the administering of glucose may come too late, or may lead to anover-reaction by the patient (e.g., administering too many fast carbs)or the patient's body (e.g. glycogen release by the body), which maythen lead to high glucose levels (sometimes referred to as the Somogyieffect). In more extreme cases, an acute risk may develop, andalternative options such as administering glucagon may be required. Inthe severe case, the patient's ability to administer or participate infollowing guidance may diminish, as the patient may lose cognitivecapacity or consciousness with very low glucose levels.

User convenience may also be accounted for in determining the timing ofguidance. For example, when it is known that a user is going to go in ameeting in 2 hours, the system may provide an alert prior to themeeting, even if the determined states or guidance are less accuratethan would ordinarily be accepted (e.g. an optimal balance of dataaccumulation and risk avoidance has not been achieved), to avoidinterrupting the user during the meeting or to assure that the guidanceis delivered at a time that an intervention can be administered. In someexamples, when the user is going into a situation where they do not wantto have to respond to an alert, the system may provide an option toreceive an alert early even if the alert or guidance may be somewhatless accurate, e.g. via a one-time user input or adjustment of auser-controlled setting, which may correlate or interact with acalendar. For example, or when the system knows or has access to thecalendar of the user, the system may on its own provide such prompts andoptions (“Would you like an early alert before your weekly Tuesdayafternoon meeting”). In another example, the system may receive arequest from the user (e.g. in the form of a user-requested insight, asfurther described below).

In some examples, a state model may be used to balance urgency andinconvenience factors. For example, states may include risk levels, orprobabilities of transitioning to an undesirable state (e.g. risk orprobability of trending to a blood glucose level below 40 mg/Dl or above180 mg/DL), and the system may control determining or delivery ofguidance to maintain risks levels or probabilities within specifiedparameters, while avoiding inconvenient notification times whenpossible.

The system may also account for user sleep schedules. For example, whenit is known that the user is going to bed within four hours of having ameal, but the glycemic response to the meal is not yet known, the systemmay provide guidance to do something before going to bed to improvetheir situation or avoid a risk of trending to an undesirable state orglucose level. For example, the system may deliver pre-sleep guidance toadminister a correction bolus, or make a basal adjustment, to avoid asustained high glucose level or a trend to a high glucose level, or toavoid waking the user for a night-time intervention. In another example,the system may deliver guidance to have a snack before going to sleep tomitigate a risk of a low glucose level.

Example Outputs—Forms of Guidance

Guidance output from the decision support engine 104 may include, forexample, text (e.g., “Watch for an unexpected low glucose level”),sounds (e.g. tones or spoken), or graphics or animations, such as apredicted or actual insulin graph, or a probability cone, which may showthe range of possible outcomes from a contemplated or consummatedaction, such as exercise, food consumption, or insulin delivery, or acombination thereof. A probability cone may show a range of potentialoutcomes over time; the range of outcomes broadens over time, i.e., awider range of options becomes possible (or may satisfy a statisticalcondition). The guidance may include alerts, recommendations, or otheruseful information.

In some examples, a guidance recommendation screen may show factorsincluded in determining guidance and may allow a user to adjustassumptions or weighing applied to each factor. For example, aninteractive recommendation may include an action to deliver four (4)units of insulin in the next 15 minutes and the set of factors used inthe decision (pasta has 40 g carbs, patient activity level after lunchis normally moderate, current glucose level is normal but falling).These factors can then be adjusted by the user if the assumptions needmodifying. In some examples, CGM insulin and meal/carb data may bepost-processed to determine best possible insulin control. In someexamples, the system may intentionally introduce a time-limited bias toreflect pending changes that are or were occurring or could occur: Forexample, the system may intentionally skew blood glucose levels low, fora limited time, right after dosing insulin to reduce the likelihood ofovercorrection.

In various examples or guidance decision-support requests may use text,email, app notifications, phone calls, or other forms of communication.In some examples, the best mode may be selected by the user or by thesystem based on the context. For example, the system may use voice whilethe patient is driving but watch messages when they are in a meeting. Insome examples, guidance and decision-support requests may be voiceenabled can using automatic speech recognition and natural languageunderstanding

Various types of guidance insights are possible. For example, theguidance output may include, for example, an event-driven insight 126, auser-requested insight 128, or a periodic insight 130. An event-driveninsight 126 may include, for example, a time, context, or physiologicevent-driven insight that is driven by an underlying algorithmidentifying a decision point, such as a useful time to deliveractionable guidance. A user-requested insight 128 may include, forexample, a user request for guidance about a particular therapy decisionat a particular time, e.g. insulin delivery before a meal or inanticipation of an event such as a meeting, physical activity, or sleep,and the decision support engine 104 may provide guidance in response tothe request. Such guidance may include, for example, a recommended basalor bolus insulin dosage or scheme, or an amount of physical exertion, ora plan to monitor or intervene at a particular time or time range. Aperiodic (non real-time) insight 130 may summarize a pattern overmultiple days, meals, or treatment decisions. For example, a periodicinsight may include a retrospective summary at the end of a period oftime such as a day, week, month, or quarter, a post-workout summary, asummary after a period of time (e.g. number of hours, or morning orafternoon or night), or variants thereof.

Example event-driven insights 126, user-requested insights 128, andperiodic insights 130 are described in further detail below.

Event-Driven Insights

A time, context, or event-driven insight may be driven by determinedstates or state transitions, physical events, location, a timing pattern(e.g. a calendar), or any combination thereof. For example, an insightmay be triggered at least in part by a physiologic event such as apattern of glycemic events, which may for example include a rapidlyfalling glucose level after a meal or during exercise, or a rapidlyrising glucose level (e.g. after a meal or snack or stressful event).

An insight may take the form of a personalized guidance message that hasparticular relevance to a presently-occurring event or pattern. Thepersonalized guidance message may be based on information that islearned about the patient, which may be embodied or reflected by one ormore models of the patient. In an example, a system may detect patternsthat precede hypoglycemic and hyperglycemic events and alert the userwith enough time to take action. In another example, a therapyadjustment may set a context-driven alarm: for example, when a therapyadjustment is made, such as an increase in basal rate, which may bedetermined to increase the risk of a night-time low glucose level, alow-glucose alert may be made more sensitive at night for a specifiedperiod of time, such as the next two weeks, or a personal guidancemessage reminding a user of the potential for a low night-time glucoselevel may be delivered each night, or more frequently or under a broaderset of conditions than prior to the adjustment. In another example, itmay be determined that a treatment decision or therapy event (e.g.forgetting to dose insulin before a meal, e.g. missed “pre-bolus”) mayjustify increased vigilance (e.g. checking of CGM data or awareness of apotential need to deliver therapy) during a time window following thedecision or event, which may be communicated via a guidance message, orduring the window a guidance message may be delivered under a broaderset of conditions (e.g. lower threshold for providing event-drivenguidance). In some examples, event-drive alerts may be set based oncumulative glycemic risk or glycemic exposure, e.g. food or caloric orcarbohydrate consumption may be tracked and an insulin/glycemicimbalance may be detected, which may be communicated via personalguidance (“Your food or beverage consumption may have exceededexpectations”) or may form the basis for a personal guidance message(“You may need more insulin based on eating or drinking patterns.”) Insome examples, a personal guidance message may provide a range ofchoices that are stratified by risk and rewards.

In some examples, the decision support engine may determine a bolusrecommendation (meal bolus or correction) and determine a time todetermine the recommendation. The timing of the determining of the bolusand delivery of the guidance may be calculated to balance the need forguidance with an interest in avoiding interruptions to the patient/userand a need for sufficient data to accurately determine bolusinformation. In an example, manual inputs and learned or planned inputs(e.g. meal information) may be fed into a bolus calculator. The boluscalculator may be a general one, or may be personalized, e.g. specifiedto the user's current diabetic state. The bolus calculator may output adose recommendation, and the system may then observe glucose levelsafter the user administers the recommended dose. Based on historicaldata, a typical glycemic response may be known for a particularsituation, which allows for a comparison of real-time data withhistorical data or a pattern derived from historical data. For example,if the user eats 60 g of carbs and takes a specific amount of insulin,the resulting glucose levels and trends that occur after time may beknown from the historical data or pattern (e.g. 120 mg/dL glucose level30 minutes after eating, and rising slowly (e.g., 2 mg/DL every 5minutes). When in a particular case, the user indicates that they ate aspecific meal or amount of carbs (e.g., 60 carbs), but glucose valuesproduce a level or a trend that is different previous profiles (e.g. 160mg/dL glucose level and rising steadily (e.g., 10 mg/dL every 5minutes), the system may then inquire with the user to obtain correctedmeal information, or determine how many carbs the user actually atebased on the glucose signal and present guidance or an inquiry (“Did youeat something else?” or “Did you not eat the chicken?”). The system mayalso account for absorption rates (e.g. fast carbs such as foods withlarge amounts or refined sugar vs. slow carbs such as pasta) and thepresence of other foods, such as protein or fat, that may affect theglucose trend, such as slowing the absorption rate of carbohydratesconsumed with the protein or fat.

In an example using state models, a patient state may initially be afirst state (e.g., eating 60 carbs), and the system may afterwarddetermine that the patient is in fact in a different state (e.g. eating90 carbs). In another example, a patient state may initially be in afirst state (eating 60 carbs), and so they dose accordingly, but thepatient state is later determined to be in state with a carb countingerror of X (e.g., 30 grams carbohydrate), and in this case the systemmay provide decision support guidance, e.g. a correction bolus, to avoida low or high.

In some examples, a time to deliver guidance regarding the correctionbolus may be determined using a physiology model, behavior model, orboth. For example, a range of acceptable times for delivery of acorrection bolus may be determined using a physiology model, and a rangeof convenient times for delivery guidance or a correction bolus may bedetermined using a behavior model, e.g., using learned patterninformation, or using calendar that shows meeting schedules or a classschedule, so that guidance may be timed for delivery between classes ormeetings, or near the end of a meeting or class.

User-Requested Insights

A user-requested insight may include, for example, receiving input froma user (e.g. through a smartphone app) for decision support for animpending diabetes decision, such as “how much insulin should I bolusbefore this meal?” or “should I have a snack before I go for a bikeride?” In an example, a personal guidance response may include aninteractive recommendation (e.g., “Deliver 4 units of insulin”) and mayalso optionally include the set of factors used in the decision (e.g.,“The portion of pasta has 40 g carbs, your activity level after lunch isnormally moderate, and your current glucose level is normal butfalling”). In some examples, the factors can may then be adjusted by theuser (e.g. to arrive at a different dose) if the assumptions needmodifying.

In some examples, a prior user-requested insight may be used as an inputto a model, and the model may learn or adapt to the circumstances when auser is likely to request insight. This information may be integratedinto the model and decision-support engine, so that the system mayprovide personalized guidance in the circumstances and time that a useris likely to need the guidance, e.g. anticipate a request andproactively provide guidance to the user. For example, if a userfrequently requests guidance before embarking on a weekly bike ride(e.g., as determined from learned behavior patterns) or dining at aparticular restaurant (e.g., as determined from a patient calendar) orafter completing a physical workout (as determined from an activitysensor, associated smartwatch, or calendar), the system may determinethat personalized guidance is likely desired at a particular time, anddeliver guidance relevant to the present situation or typical pattern.User-requested insights may also be used to educate a model, based uponinformation implicit in the user request. For example, when a user asksfor decision support prior to exercising, the system can glean that theuser tends to exercise at a particular time, especially when a series ofrelated user requests are obtained over a time period, which may revealan exercise timing pattern (e.g. running on Monday, Wednesday, andFriday mornings).

In some examples, the system may receive a user request for decisionsupport for a future activity (e.g., exercise, driving, meal, or sleep),and the system may provide suggested therapy adjustments or preparatorysteps as guidance. For example, the guidance may include changes inbasal insulin, bolus insulin calculations, and suggested snack amounts(e.g., change your basal rate by x amount before you begin exercising,or eat 15 grams of carbs before you go to sleep). In some examples, thesystem (e.g. model) may learn from the result of the guidance, and makeadjustments specific to the individual, e.g., the system may learn howmuch exercise changes their glucose. In some examples, patient-specificinformation, such as basal rates, or insulin-to-carb ratios forspecified meals or times of day, may entered by a clinician into anelectronic medical record (EMR) system and retrieved by the system andused to inform or educate the model or assist with developing responsesto patient requests for guidance.

In an example, the system may receive a user request for pre-sleepguidance. The request may, for example, be received through adecision-support smartphone app. The system may provide guidanceregarding one or more actions the user should perform or consider beforegoing to sleep, such as eating a snack, delivering a dose of insulin,setting an alarm clock, or setting an alert setting for a continuousglucose monitor. The system may also provide an explanation of a risk ora reason for guidance. For example, the system may notify the user of arisk of a “late low” glucose level due to an exercise session, or a riskof a low glucose level due to a reported insulin dose that the systemestimates was too large for a given meal or set of circumstances, or arisk of a low or high glucose level based upon a trend analysis. In someexamples, the system may notify the user of a time or time range that aproblem may occur, such as “A low glucose level may occur aroundmidnight.” In some examples, the system may suggest that the userre-check guidance (e.g., check a smartphone decision support app forupdated guidance) at a later time, which may occur for example when thesystem determines that additional information (e.g., additional CGMtrend data) may be particularly useful in determining guidance,increasing confidence in guidance, or determining an expected event.

In an example, a user may supply a photo of an upcoming meal, or scan arestaurant menu, and the system may provide guidance about an estimatedeffect on blood glucose or an insulin dosing recommendation. Forexample, a mobile device (e.g., smartphone) application may beconfigured to scan a menu and convert the meal items into estimatedglycemic impact. in an example, a user may be prompted to position asmart device camera over a menu, and the glucose information for themenu item may be presented on a user interface, e.g. next to a menu itemas viewed by a user on a screen. This may be accomplished, for example,using text recognition and a lookup table of glucose values for aparticular type of meal or establishment. In some examples, meals thatwould be considered “healthy” or “unhealthy” may be highlighted,indicated with text or symbols, or otherwise identified on the userinterface or, e.g., using augmented reality (AR) where a menu is thesubject of augmentation. in some examples, a predicted glycemic impactor excursion (e.g., “72 g. carbs” or “BG>200”) or necessary insulinbolus (e.g. 6 units) may be presented. In some examples, a predictedtrend graph, or summary metrics such as glycemic load, may be presented.In some examples, a predicted excursion may be personalized by learningfrom historic data or profiling the patient, and optionallyincorporating such information into a physiologic model, so that theimpact on glucose is personalized to the patient. In another example,when a proposed workout (e.g. 30 minutes of moderate running, or fivesets of dead lifts, or 1 hour of swimming) is provided as input (e.g.entered into a smartphone app), the expected result, such as a glucoseprofile, may be predicted (e.g. by applying the workout as input to amodel) and displayed on the user interface. The result may, for example,be provided as a probability cone to provide the user with informationabout the potential range glycemic responses.

In some examples, guidance may include a bolus recommendation that mayinclude two numbers to reflect a decision tree, e.g. one bolus numberthat assumes the user exercises as planned, and a second bolus numberthat assumes that the exercise is not completed. In some examples, theguidance may include an amount of insulin on board, which may be theamount of insulin determined to be active in the body as determined bypredefined algorithm (e.g. based on population-based or theoreticaldata), or as determined by a model (in which case the insulin on boardmay be patient-specific). Insulin on board guidance may be provided inresponse to a user request, or in response to an event, such as adetermination that the insulin on board is likely to cause a low glucoselevel, or a determination that the amount of insulin on board is likelyto be insufficient to control glucose levels (i.e., a high glucose levelmay occur). In some examples, guidance may reflect a preset oruser-defined goal, such as a predefined blood glucose range (e.g.,70-150 mg/dL range) or a percent of time that the glucose level is in adefined range (e.g. 80% in the 70-150 mg/dL range). For example, theguidance may include a suggested modification (e.g. afternoon exerciseor an insulin dosage change) to move the user toward the goal.

In another example, input from a user may initiate a glucose tolerancetest or other type of self-evaluation, e.g. where a well-characterizedmeal is eaten and the glucose response is tracked. A result of the testor evaluation may be communicated via a guidance message (e.g. “Yourblood glucose stayed in range” or “Your blood glucose spikedquickly—consider a longer pre-bolus time”.

Periodic Insights

Periodic insights may also be provided as guidance. For example,guidance may be provided as on a periodic schedule, such as a weeklyupdate, or when it is determined that sufficient data is available toprovide a reliable summary, such as 10 low-carb breakfasts versus 10high carb breakfasts to provide comparative analysis, averages, graphs,probability zones, or other information about diabetes management. In anexample, meals or foods may be grouped by types with a similar glycemicresponse in terms of magnitude and time course (‘spikes versus slow’).In another example, meals or foods may be grouped by similar insulindosing strategies, such as which meals needed correction boluses. Inanother example, the decision support engine may summarize the type ofdecisions that have unreliable outcomes in a manner that encourageseducation (‘ideas for low-carb breakfasts’) or medical review (e.g.,inquiry to a doctor about strategies for management). The decisionsupport engine may compile a summary of such information (e.g. problemmeals) in anticipation of a doctor visit including successes andconcerns.

In some examples, the decision support engine may provide schedule-basedtrend information. For example, a person's schedule may differ onweekends vs weekdays. This schedule difference may be reflected in thepatient's glucose levels, or the patient's interest or availability inmanaging glucose levels, or the patient's goals or thresholds fornotification. In some examples, periodic insights may be presented in amanner that differentiates based on schedule, e.g. weekend trends andweekday trends may be presented separately. Guidance may also includedistinct therapy or behavior suggestions for different portions of aperson's schedule, e.g. different basal patterns may be suggested basedon knowledge of schedules. In various examples, the schedules arelearned by a model, informed by a patient or caregiver calendar, basedon user input via a user interface (e.g. answering questions on asmartphone), or combinations thereof.

The various insight examples described above may be translated to adifferent type of insight, e.g. an example described as an event-driveninsight may be provided as a user-requested insight, and auser-requested insight may be provided as an event-driven insightthrough application of an algorithm or model to determine conditions andtiming of delivery of the insight as guidance.

“Real time” does not necessarily mean immediate, but allows forintervention based on recent data or trends to affect near-termoutcomes, as opposed to retrospective information presented to evaluateoverall behavior or opportunities for therapy improvement.

Interaction of Inputs and Model(s)

FIG. 2A is an illustration of an example configuration of the model 110shown in FIG. 1. FIG. 38 is a diagram showing another example of thearrangement showing FIG. 2A. The patient 102 has an interest incontrolling the true glucose level 160, which may be measured by asensor 152. The physiology model 112, behavior model 114, andmeasurement model 116 process inputs and generate outputs (e.g.,states), which may be provided to the patient as guidance, or may beused to determine guidance for the patient 102, as well as a time todetermine or deliver the guidance. Guidance may be delivered via aguidance module 150.

A sensor system 152 may measure physiologic parameters such as a glucoselevel, activity, heart rate, respiration, or body temperature orcontextual parameters such as ambient temperature, pressure, orlocation. The sensor system 150 may include a plurality of sensorsintegrated into a single device (e.g. a watch), or a group ofmulti-sensor devices (e.g. a watch and a wearable sensor), or thesensors may reside in individual discrete devices, which may or may notcommunicate with each other. For simplicity, the sensors that providedata inputs are simply referenced as a “sensor system.” The sensorsystem 152 may include a continuous glucose monitor (more detailprovided below) that may be configured to measure a glucose level thatis calculated to be indicative of the true glucose level 160.

Data from the sensor system 152 may be provided as input to thephysiology model 112 or the behavior model 114, or both. The physiologymodel 112 may also receive input from the patient 102, input from ameasurement model 154 (described below), input from the behavior model112 (such as activity state or stress state), or information aboutmedication delivery 156 (e.g., insulin delivery), which may be receivedvia user input from a patient or from a delivery device such as aninsulin pump or insulin pen. The physiology model may also use otherinputs. A detailed description of the physiology model inputs andoutputs is provided below in relation to FIG. 2B, and numerous inputsare shown and described in FIGS. 14-16. The physiology model may providephysiology state information as output, such as a current or projectedglucose level or trend, insulin to carb ratio (ICR), insulin sensitivityfactor (ISF), basal rate(s), or insulin on board (JOB), all of which mayimpact the true glucose level 160 and insulin delivery decisions orrecommendations made by the guidance module 150 or the patient 102 or acaregiver or clinician.

The physiology model 112 or behavior model 114 may also receiveinformation received from the patient, such as calendar information froma computer system such as a smart phone, or user input about specificactivity or exercise, or user input about food consumed. The behaviormodel may also receive as input the guidance information delivered tothe patient, as well as sensor data. The behavior model may also receiveoutput from the physiology model. The behavior model may process thevarious inputs to determine a current patient state, or anticipate afuture patient state, which may include, for example, exercise, sleep,availability for intervention, interest in receiving guidance, and otherinformation about patient activity, interests or behavior. The behaviormodel may also receive contextual information or determine present orprojected contextual information as a state (e.g. in a meeting ordriving home), which may be used to determine guidance, or the timing ofdelivery of guidance. A detailed description of the behavior modelinputs and outputs is provided below in relation to FIG. 2B, andnumerous inputs are shown and described in FIGS. 14-16. A measurementmodel 154 may optionally be included in the system. Data from the sensorsystem 152 may be provided to the measurement model 154, which mayprocess the sensor data to assess the accuracy or precision of the data,e.g. to determine a likelihood that a measured glucose level matches atrue glucose level. The sensor system may use statistical methods suchas variability or variance of sensor data points, trend information,historical information, as well information provided by the behaviormodel, physiology model, and other sensors, to assess whether one ormore sensor data points are likely accurate or inaccurate. For example,when successive blood glucose data vary widely or reveal patterns thatdo not reflect normal physiological patterns (e.g. 90 mg/dl, 112 mg/dl,96 mg/dl, 121 mg/dl in successive five-minute increments), themeasurement model may determine that sensor data is relativelyinaccurate. Other sensor data may also be assessed. Sensor data may beevaluated based on the data being outside a range of probable values.For example, if an ambient temperature is detected as −5 Celsius inJuly, the model may conclude that the sensor reading is inaccurate,especially if location information is available. In another example,activity information may be processed, including correlating measurementmodel aspects with behavioral model aspects, to determine correlation tolikely actual activity. For example, accelerometer information may beprocessed to assess whether motion is overly rhythmic (which mayindicate mechanical motion, e.g. a bumpy ride, as opposed to exercise)or outside a probable range (e.g. a relatively sedentary person beingactive for three hours.) Output from the measurement model (e.g.accuracy state information) may be provided to the behavior model 114 orphysiology model 112 for integration with other information to determinephysiology or behavior states.

The guidance module 150 may deliver guidance information to the patient102, for example via a user interface on a mobile device such as a smartphone. In some examples, the guidance module 150 may determine theguidance based on information (e.g. states) provided by the physiologymodel 112 and behavior model 114, and may determine a time to providethe guidance that is calculated to be useful to the patient. In otherexamples, the guidance and delivery time may be determined by a model,e.g. the behavior model 114, and the guidance module 150 may provide thedetermined guidance at the determined time. In various examples, theguidance module 150 may, for example reside on the mobile device 108, ormay reside on a computer system, which may be remote from the patient orlocal and deliver guidance to the patient through a user interface onthe mobile device 108 or another device.

Example Models

FIG. 2B provides a more detailed illustration of example model inputsand example states that may be determined by applying inputs to a model.The physiology model 112, behavior model 114, and measurement model 116of FIG. 2B are shown, along with example inputs and states for eachmodel. Example inputs are shown in the left, and example determinedstates are shown in the right. FIGS. 14-16 below provide a morecomprehensive recitation of inputs, any of which may be applied to oneor more of the models. States may be identified by a physician or expertor learned by the model via machine learning. Each state may have two ormore (and possibly a multiplicity) of state values, e.g. discretenumerical values, ranges, or qualitative values (high/medium/low orstable/unstable.) The states may be determined by applying one or moreof the sources of input data to a model. While three models are shown,one skilled in the art would understand that the models may beintegrated into one or two models, or broken into a larger number ofmodels or sub-models.

Physiologic Model

Food consumption may be provided as an input to the physiology model112. The food consumption information may include information aboutmeals, snacks, and beverages, such as the size, content (carbohydrate,fat, protein), sequence of consumption, and time of consumption. Foodconsumption may be provided by a user through a via manual entry, or byproviding a photograph through an application that is configured torecognize food types and quantities, or by scanning a bar code or menu.In various examples, meal size may be manually entered as calories,quantity (‘three cookies’), menu items (‘Royale with Cheese’), or foodexchanges (1 fruit, 1 dairy). In some examples, meals may also beentered with the user's typical items or combinations for this time orcontext (e.g. workday breakfast at home, weekend brunch at restaurant).In some examples, meal information may be received via a convenient userinterface. For example, as shown in FIGS. 25A and 25B, a user interface2500 may enable a user to indicate on by touching a graph 2502 (or othergraphical user interface element) an amount of fat and carbohydrate (andoptionally additionally protein) in each meal. FIG. 25A shows a selectedpoint 2504 on the graph 2502 with high carbohydrate (78 grams) and lowfat (1.6 gram) content. FIG. 25B shows a selected point 2506 on thegraph 2502 with high carbohydrate (78 grams) and low fat (1.6 gram)content. FIG. 25B shows a selected point 2506 on the graph 2502 with lowcarbohydrate (3 grams) and relatively high fat (20 gram) content.Example meals with similar nutritional content (e.g. carb to fat ratio)may be shown on the user interface.

Activity may also be provided as an input to the physiology model.Activity information may be provided, for example, by an accelerometersensor on a wearable device such as a watch, fitness tracker, or patch.

Patient statistics, such as age, height, weight, body mass index, bodycomposition (e.g. % body fat), stature, build, or other information mayalso be provided as input, through a user interface, or by interfacingwith an electronic source such as an electronic medical record, or frommeasurement device such as a wireless, e.g., Bluetooth-enabled, weightscale or camera, which may, for example, communicate with the mobiledevice 108 to provide patient data.

Insulin delivery may be received by the model, via a wireless connectionon a smart pen, or via user input or from an insulin pump. Insulindelivery information may include insulin volume, and time of delivery.Other parameters, such as insulin action time or duration of insulinaction, may also be received as inputs.

The physiology model 112 may also receive user input through a userinterface, such as on a smart device 108. Such user input may includemental state or stressor information, the delivery of therapy, such asthe use of glucagon to stimulate liver release of glycogen in responseto a low blood sugar, recommended basal rates or insulin-to-carb ratios(e.g. received from a clinician), or recorded activity (e.g. intensity,duration and time completed or started).

Input may also be received from sensors, such as physiologic sensors,which may detect heart rate, respiration, oxygen saturation, or bodytemperature (e.g. to detect illness). Electromagnetic sensors may alsodetect low-power RF fields emitted from objects or tools touching ornear the object, which may provide information about the patientactivity or location. Glucose level information may also be provided asinput, for example through a continuous glucose monitoring (CGM) systemthat provides CGM data. Input may also be received from smart pilldispensers that track when customers take medicine, a blood ketonemeter, a laboratory-measured or estimated A1C, other measures oflong-term control, or sensors to measure peripheral neuropathy usingtactile response, such as using haptic features of a smartphone, or aspecialty device.

States from the measurement or behavior model may also be provided asinput.

Time may also be provided as an input, such as time of day, or time froma real-time clock.

In some examples, model inputs may be inferred, e.g. from one or more ofhistorical user inputs (e.g. a meal diary), geolocation, insulin dosing,CGM features (rising blood sugar), or time of day. In some examples, themodel may operate in a learning mode, where a database of information(historical or real-time) is collected. Causes or effects or both may bededuced from the database. Patterns may also be deduced from thedatabase, such as patterns associated with certain meals or meal typesor activities, or insulin action time or duration of insulin action, orcombinations thereof.

Physiologic States

One or more physiologic states may be determined by applying inputs tothe physiology model. Metabolic rate may include a basal metabolic rate(e.g., energy consumed at rest) as well as active metabolism, e.g.energy consumed by activity, e.g. exercise, activity, or exertion. Insome examples, basal metabolic rate and active metabolism may be trackedas separate states. Activity level may also be determined, for examplebased on an activity sensor or other physiologic sensors. The activitylevel state may, for example, include four states: sleeping, resting,active, exercising. Insulin sensitivity may be determined usinghistorical data, real-time data, or a combination thereof, and may, forexample, be based upon food consumption, insulin delivery, and resultingglucose levels. Insulin on board may be determined using insulindelivery information, as well as known or learned (e.g. from patientdata) insulin time action profiles, which may account for both basalmetabolic rate (update of insulin to maintain operation of the body) andinsulin usage driven by activity or food consumption. Meal state mayinclude, e.g. fasting, premeal, eating, post-meal response, or stable.Meal state may also include nourishment on board, e.g. meals, snacks, orbeverages consumed, and may be determined, for example from foodconsumption information, time of meal information, and digestive rateinformation, which may be correlated to food type, quantity, andsequence (e.g., which food/beverage was eaten first.) Health andsickness may be determined, for example, based on user input (e.g.pregnancy information or known sickness information), from physiologicsensors (e.g. temperature), activity sensors, or a combination thereof.Example health states may include, for example, health, illness, rested,and exhausted. Glucose level may be determined from sensor information(e.g., CGM data), optionally in combination with the measurement modelstate. In some examples, a glucose level state may also be determinedfrom the model when CGM data is not available or is of uncertainreliability, for example based upon historical information about glucoselevels in particular situations, e.g. given a combination of foodconsumption, insulin, and activity. Degree of glycemic control (notshown) may also be determined as a state, and may be based, for example,on glucose levels, variation in glucose level, or insulin dosingpatterns. Confidence levels may be applied for one or more of the states(e.g., high, medium, low, or numerical confidence.)

In some examples, transitions between states may be important decisionspoints for determining guidance or a time to determine or deliverguidance. For example, a user may especially need guidance attransitions between states. For example, guidance may be needed whilewaiting for the glucose response after a meal, or deciding what to dobefore exercising. These state transitions, or projected statetransitions, may be identified by a system (e.g., using a model) andused to determine a time to determine or deliver guidance. Examples ofthese states transitions may include Active→resting→exercising→sleeping,or Health→illness→rested→exhausted, or variations in degree of glycemiccontrol (e.g., glucose level variation, variation in insulinsensitivity, insulin dosing changes), or a transition to pregnancy. Insome examples, the physiology model 112 also includes a disease stagestate, such as for Type II diabetics. Example disease stage states forType II diabetics can include a prediabetic stage, an oral treatmentstage, and a basal insulin treatment stage. Insights provided by thedecision support engine may vary for hosts in different disease stages,for example, as described herein.

Modeling Kinetic and Potential Energy Flows

In an example, the physiology model 112 may characterize the flow ofenergy in the human body, which may include the effect of meals,exercise, glucose and insulin, as well as other hormones such ascortisol and adrenaline. Energy inputs may include meals and snacks(characterized by time, size, and type), and glucose production by theliver (e.g., the “dawn effect” where the body releases energy in earlymorning, or the release of energy by the liver to counter a low bloodglucose level). Energy outputs may include energy consumption fromactivity, such as exercise, and glycogen replacement by muscles or theliver, and glucose uptake driven by insulin. Insulin timeaction-profiles may be taken into account as well as the separateimpacts of the basal (e.g. resting) metabolism and active metabolism(e.g. from activity/exercise). The model 112 may be tuned to a subject'sphysiology using user-inputs, measurements (e.g., CGM patterns andfitness tracker or accelerometer) and inference, e.g. the learning ofpatterns and associations from data.

At a high level, the physiologic model may track energy inputs, energyoutputs, and determine one or more physiologic states. Thisenergy-characterizing aspect of the physiology model may be used topredict future glycemic states (e.g. high glucose level, low glucoselevel, rising glucose trend, falling glucose trend). The physiologicmodel may also interact with the behavior model and a guidance module(e.g., decisions-support app) to determine when the user is likely toneed context-specific guidance (e.g., advice, alerts, or warnings), suchas during a transition from resting to exercising, or from healthy tosick.

Behavioral Model

A behavior model may reflect the behavior, preferences, schedule, andother information about the user. Referring again to FIG. 2B, the inputto the behavior model may include user input, such as input through auser interface regarding activity, level of interest in guidance, orlocation. Input to the behavior model may also include calendarinformation, such as availability or activity information received froma computer or smartphone calendar application. The input may alsoinclude activity, such as information from an activity sensor such as anaccelerometer on a watch or fitness band. Inputs to the behavior modelmay also include location (e.g. GPS), time (e.g. from a real-timeclock), prior guidance to a user, and the physiology state. Additionalinputs are also possible.

Behavior model states may include availability or convenience ofintervention (e.g. available/not available or convenient/not convenient)which may be deduced from a calendar or inferred schedule or from alearned pattern of a patient or caregiver schedule. Availability orconvenience states may also include the proximity of caregiver to apatient, which may be inferred from location information or calendarinformation.

Behavior model states may also include risk tolerance (e.g. comfort withtrends toward low blood glucose levels, which may depend on experiencewith intervention or the availability of caregivers for intervention),interest in guidance, activity state, (e.g. exercising or not, which maybe inferred from a calendar or activity sensor), sleep state (e.g. sleepor resting or awake, which may be inferred from an activity sensor,calendar, or other information), appetite (which may be inferred forexample from meal patterns),

Engagement (or level of engagement) may also be determined as a behaviormodel state. For example, engagement factors may include user responseto decision support, in terms of time, activity, and type of support(user-requested, context generated, periodic). Engagement states mayinclude, for example, the type of guidance that tends to prompt action,the actions that a user participates in, which may be correlated totime, (e.g., can't take a walk 9 to 5) or activity (e.g. no finger-prickblood glucose tests while running). A level-of-engagement state may alsoreflect the time a user is engaged in receiving or following guidance(e.g. where shorter times suggest guidance is disregarded). Theengagement state may also include the type of communication, which maybe correlated to activity or schedule, such as learning an appropriatemode to interact with a user depending on the time of day and location.For example, a user may get watch or phone display messages in ameeting, voice messages in the car, and tiered messages based on urgencywhile sleeping, where urgent message are accompanied with a sound orvibration and less-urgent messages quietly appear on a display or watch.In some examples, level-of-engagement logic and schemes applied abovemay also be applied to caregivers (e.g. data followers on smartdevices), to inform them of needs for intervention, or to let them knowthat the patient or another caregiver is aware of or managing thesituation.

A level-of-concern state may also be determined by the behavior model.For example, the system may determine situations that may create concernabout the current physiologic state, the consequence of treatmentdecision, or potential future states, and determine a level of concernbased upon the presence or absence or likelihood of such situations. Forexample, the manner in which a patient views CGM values or guidance, orthe device on which they view the information, how they view it (e.g. ona watch, or phone, or interactions with a full screen view or only anotification screen that may provide less information) may indicate alevel of concern (where seeking of more information or less convenientinformation indicates more concern). The frequency with which a CGM dataor guidance is checked or requested, or when the user stops checking,may also indicate a level of concern (more frequent indicates moreconcern. Other factors that may be accounted for in determining a levelof concern may include self-monitored blood glucose readings (e.g.finger prick sensor readings), requests for decision support and thecircumstances surrounding such requests (e.g., restaurant meal versushome cooked), when insulin adjustments are made (basal, prandial,postprandial), the consumption of a snack or fast-acting carbohydratesto avoid lows, the presence or attention of caregivers (e.g. datafollowers) who watch glucose levels or responds to data updates, orpatterns of alarms. In some examples, level of concern or alarmpreferences may be learned through a model or set through user inputbased on real or hypothetical data, as shown in the example userinterface 2602 shown in FIG. 26.

Level of concern state may be based on time periods when a user isconcerned (e.g., time of day, or a period of time after a meal, or aperiod of time after exercise, or certain days of the week or days ofthe month, or times derived from calendar events, e.g. holidays orschool events.) Time periods may also be applied to care givers (e.g.data followers). The level of concern for time periods may, for example,be derived from user input, or learned from user behavior. Level ofconcern may also reflect the user's goals, e.g. the level of userconcern with alarms and lows, or focused on maximizing the timein-range, or both.

The behavior model may also include a guidance state, which may includefor example an insulin guidance state (e.g. deliver X units of insulin,or increase/decrease basal rate), and a carb consumption guidance state(e.g. eat X grams of carbs).

In some examples, the generation of guidance messages or otherinformation for the patient may be conducted as part of the behaviormodel (e.g. as output states from the model.) For clarity and simplicityof description, guidance generation is described separately below.

Measurement Model

A measurement model may provide information relating to sensormeasurements, such as CGM sensor measurements. The measurement modelmay, for example, provide an indication of the accuracy of data from asensor.

A CGM measurement model may add context to the glucose values andpatterns generated from sensor data. The model may allow for differentdata types. For example, confidence bounds may be determined for datavalues or a data set. The confidence bounds may be presented to the useror provided as input to another model. The model may, for example,provide accuracy bounds that adjust for day of use (e.g., freshlyimplanted sensor vs. aging sensor, which may become inaccurate),adherence to calibration schedules, the impact of lag at high rates ofchanges (both due to physiologic lag in the movement of glucose levelsin interstitial fluid, and sensor lag because the sensor only takes areading periodically, e.g. every 5 minutes. The measurement model mayalso monitor for consistency between the blood glucose and CGM readings,as an indicator of the reliability of a blood glucose reading, CGMreading, or both. Similar principles may be applied to other sources ofdata to assess accuracy, consistency, or variability.

With reference to FIG. 2B, the measurement model may receive user input,sensor data, and calibration information as input, and may determinemeasurement states such as sensor accuracy (e.g. high, medium, low),confidence in sensor data, or sensor status (e.g. warmup/active status,time since insertion or time until replacement, or sensor connectivity.)Other sources of measurement model input data may include dataconfigured to allow for factory calibration or non-user interventioncalibration.

Determination of Timing of Guidance

In various examples, guidance, and the timing of guidance, may bedetermined based on state models or other inputs. For example, guidancemay be determined from one or more physiologic states or behaviorstates, or a combination thereof. The timing of determining of guidanceor delivery of guidance may also be determined from physiologic andbehavior states. In some examples, a plurality or multiplicity of statesmay be used to determine guidance, and the timing of guidance. Invarious examples, the guidance, and timing of delivery of the guidance,may be made by the behavior model, or by a guidance module that usesstate information such as states from the behavior model and physiologicmodel.

Learning

In some examples, the system may enter a “learning mode” in which thesystem observes physiologic or behavior data. For example, the systemmay collect CGM values, blood glucose measurement, insulin doses, food,activity, medication, stress levels, sleep patterns, hormone cycles,location (via GPS, etc.) and other information to build an informationset from which patterns may be deduced. The system may, for example,determine basal dose, insulin sensitivity, insulin-to-carb ratio,insulin duration of action, or bolus for commonly used meals. In anexample, protocols may be followed, in cooperation with patientinvolvement, which may include tracking factors such as ingestion ofcarbohydrates and insulin administration. The resulting glucose levelsor trends may be determined for a patient, especially if the patient isnewly diagnosed or treated. Some factors, such as insulin sensitivity,vary throughout the day, so in some examples a protocol may be followedseveral times at different times of day to obtain correlations betweenthe desired parameter (e.g., insulin sensitivity) and time of day. Acarb-to-glucose ratio may also be determined, for example by determininghow much a patient's glucose level increases per one gram ofcarbohydrate, and accounting for an underlying basal rate.

In an example, for basal a test, a user may be asked to pick a day whentheir BG is in a specified range (e.g., between 80-250), plan to skip ameal, control their diet so a previous meal is not high fat or very highin carbs, and avoid exercising or doing anything else that might affecttheir blood glucose. A system may receive an input from a user toinitiate a basal test. The system may then evaluate blood glucoseconcentration levels for a period of time (e.g., three hours) after thelast meal. If the blood glucose levels are stable through the period oftime, the system may declare that the basal rate(s) are correct. Ifthere are periods of time when the BG is increasing or decreasing, thenbasal rates affecting that period of time may be modified by small, safeincrements, until the blood glucose is stable over the whole period. Insome examples, this process may be repeated until a full 24-hour period(or longer, e.g. a week) has been covered by a successful basal test.

For an insulin-to-carb ratio test, a user may be asked to pick a timewhen the blood sugar is in a specified range (e.g., between 80-250), atleast a specified amount of time (e.g., four hours) from their previousmeal, at a time not affected by exercise, stress, or anything else thatmight affect blood glucose, and eat a specific meal with known carbcontent and moderate glycemic index. In some example, the system mayrequest that the user eat specified foods or ask the user to consumefood with a nutritional label and take a picture to confirm. Because thecarb content is established with confidence and other sources of glucosevariability is minimized, the system can determine an ICR for thepatient. In some examples, the process may be run multiples to enablethe system to hone in to the correct ICR. This may be achieved, forexample, by making small, safe, run-to-run changes until the mealcontent is adequately covered (i.e. until the system identifies anappropriate insulin dose that produces stable glucose levels in a desirerange).

In another example, to estimate an insulin sensitivity factor (ISF), auser may be asked to pick a time that is a specified amount of time(e.g., 4 hours) after the last meal, and to avoid exercise and otherbehaviors that may affect glucose levels. The system may then ask theuser to take a correction bolus. The system may then monitor the glucoseresponse and use the response to determine an insulin sensitivityfactor. In some examples, the process may be repeated two or more timesuntil a correct ISF value is determined.

In some examples, basal rates are determined first, to enable accurateestimate of ISF and ICR and ISF. In some examples, a decision-supportsystem may determine appropriate periods to determine basal rates, ISF,or ICR, instead of or in addition to requesting patient involvement orcooperation.

The system may integrate various states and learn the inter-relation ofstates. For example, the system may track exercise intensity andduration, glucose levels, and insulin dosages, and learn how exerciseimpacts glucose sensitivity. A determined glucose sensitivity may beprovided as guidance or may be used to determine other states or as aninput to an algorithm to determine guidance. The system may alsoreference or build nutritional databases and link the database to apatient (e.g. track how a patient responds to specific meals or types offoods). The system may also track insulin sensitivity, and pattern ofinsulin usage, for example, to predict insulin sensitivity changes orinsulin usage patterns. The system may also track a recent history ofglycemic control, which may be used to predict future control, or stressresponse of a user, which may impact insulin sensitivity (e.g., the bodyreleases cortisol in response to stress, which makes the body insulinresistant.)

In an example, the system may learn when a patient makes a treatmentdecision, and how the patient and caregivers (e.g. data followers on asmartphone) track the outcome of the decision. The system may thenanticipate when a patient is likely to make a similar decision, and whatinformation would be useful in making the decision and provide suchinformation as guidance. The system may also anticipate a desiredoutcome, and then either provide a confirmatory notification (e.g. “Goodjob! Your post breakfast peak was 140 mg/dL and now you are stable andin range”) or recognize that the desired outcome has not been achieved(“After your 3-unit bolus at 7:00 am you are still at 220 mg/dL andrising”).

In some examples, the system may identify a situation or pattern ofinterest (e.g., a common situation, such as a meal, exercise regimen, orholiday), or receive identification of such a situation or pattern froma user and develop a more effective or more accurate guidance or timingof guidance for the identified situation. For example, the system mayobtain information about the identified situation by requesting userinput, or by supervising an “experiment” to enable collection of alarger volume of data or more accurate data. The additional data may beused improve guidance or timing of guidance for the identifiedsituations.

States

In some examples, the content and timing of guidance may be determinedby states. For example, it may be determined to deliver guidance toconsume carbs when in response to the occurrence of a specified glucosestate, such as a glucose level or trend satisfying a specifiedcondition. In some examples, a state may be based on a combination ofparameters, such as exercise and glucose. For example, a “low glucoseexercise” state may correspond to a glucose level satisfying a condition(e.g., glucose level below a threshold) and exercise being anticipated(e.g., from a pattern or calendar) or exercise being detected (e.g.,from a physiologic sensor or accelerometer.) In some examples, a modelmay be based upon a plurality or multiplicity of states. For examples, amodel may include one or more of a glucose state, an exercise state, ahealth/sickness state, a sleep/wake state. In some examples, a systemmay combine or use a plurality of models to determine guidance, and whento deliver guidance.

In some examples, state transitions may be detected using the model, andused to generate guidance or notifications to the patient. Somephysiologic state transitions (e.g. sickness/health) may occur over thetime period of days or weeks, whereas others may occur in hours orminutes (e.g. glucose level or trend). In some examples, guidance may bedelivered when a state transition condition is satisfied. For example,when a patient is trending to a low glucose level and transitions to anexercise state or is determined as likely to exercise soon (e.g., usinga pattern or based on location at a park or gym), guidance may be givento consume some carbohydrates. In some examples, a combination of statetransitions may trigger guidance (e.g. transition from normal glucose tolow glucose and a transition from sedentary to active/exercising state.)

The probability of state transitions may be used to determine guidance,or whether and when to deliver guidance. For example, when a probabilityof a transition to an undesirable state is detected, guidance may bedetermined and delivered. In some examples, the guidance may bedetermined and delivered only if one or more additional conditions aresatisfied, e.g. when an availability state or a level of concern statemeet specified conditions.

In some examples, the system may deliver guidance when a specifiedcombination of state conditions is satisfied, or a specified combinationof state transitions has occurred, or is calculated to be likely tooccur. For example, guidance may be delivered when both a glucose stateand an exercise state satisfy specified conditions, e.g. guidance may bedelivered when a low glucose state is present or likely, and a patientis about to exercise, or just completed exercising. In some examples,the system determines a messaging frequency for providing insight orguidance based on a state condition or conditions, such as the host'sengagement state.

In some examples, the system may adjust the guidance based on theseverity of the situation, level of concern and level of engagement. Forexample, a determination of whether to withhold guidance or deliverguidance may be determined in part based on the level of concern stateor level of engagement state of the behavioral model at a particularpoint in time. Where level of concern or level of engagement arerelatively low, delivery of guidance may be deferred until a time whenthe user is more available, or a time that is more convenient for theuser. In a situation where a level of concern or level of engagementstate is high, guidance may be delivered even though it may be at a timethat is inconvenient. For example, guidance regarding an emergentsituation may be delivered even though a user is in a meeting, butguidance about a relatively routine (e.g., low concern/engagement)problem may be deferred until after the meeting. In this way, themessaging frequency of insight and/or guidance delivered to hosts withengagement states indicating low levels of engagement may be reduced.This may prevent low-engagement state hosts from being overwhelmed withguidance. As the host's level of engagement changes, the frequency ofguidance may also change. For example, the host may respond to initiallow-frequency guidance by becoming more engaged—e.g., reaching anengagement state indicating a higher level of engagement. If thisoccurs, the frequency of may be increased. For example, the delivery ofguidance may not be deferred and/or may be deferred for a smaller amountof time than when the host is in engagement states indicating lowerlevels of engagement. If the host's engagement state changes to indicatea lower level of engagement, the frequency of guidance delivery may bedecreased.

Guidance Examples

In various examples, guidance is determined based at least in part ontime. For example, the determining of guidance may be based on clocktime, or time of day (e.g. zones, such as morning, afternoon, evening,night). Insulin sensitivity tends to vary based on several overlappingfunctions of time. For example, diabetes patients tend to be moreinsulin resistant in the morning due to factors such as other hormonessecreted by the body in the morning. The determining of guidance may bebased at least in part on time of day to account for time-varyinginsulin sensitivity. The determining of guidance may also vary with timebased upon patient behavior, such as exercise routine and daily eatinghabits and eating schedule. Other physiological parameters (e.g.,stress, alcohol consumption, heat exposure, adrenaline-inducing eventssuch as sporting competitions) may also have a dependence on time.

In various examples, determined guidance may include guidance on how torespond to a specific situation (e.g., a detected or predictedhypoglycemic event or hyperglycemic excursion) or more general guidanceregarding therapy or behavior (e.g., a change to insulin to carb ratiofor a particular meal (e.g., lunch) or to get exercise in a particulartimeframe (e.g., “consider a quick walk after breakfast to increase yourinsulin sensitivity”).

In some examples, information determined from the physiology model orthe behavior model may be used to propose alternate approaches to commonpatterns. For example, the system may determine that user has a tendencyto over-correct or under-correct in a particular situation, e.g. at aparticular time or after a particular meal, and guidance may be providedwhen the system detects the pattern associate with the correction error.In some cases, the system may simulate what would happen with alternatetherapy approaches or compare historic approaches. For example, analternative approach may be provided as guidance after anover-correction or under-correction has occurred. In another example,predictive trends may be presented for a proposed behavior. For example,a user may enter via a user interface a proposed insulin dose or snackor meal, and the system may display a predictive trend. In an exampleillustrated in FIG. 27A, a user may be presented with a user interface2702 that includes a scrolling dial 2704 that may allow for selection ofa carb amount, and the system may present a predictive trend 2706 thatshows the likely outcome from a snack containing the selected amount ofcarbs. In another example, illustrated in FIG. 27B, a user may enter aproposed carb value, a proposed insulin dose, and the system may presenta user interface 2720 that shows three curves, one curve 2708 for ascenario where carbs are ingested but no insulin is administered, one2710 for a scenario where insulin is administered but no carbs areingested, and an estimated glucose value curve 2712 for a scenario whereboth glucose and insulin are administered. In some examples, the dialshown in FIG. 27A may be provided on the user interface 2720 shown inFIG. 27B. While the predictive insulin trends are shown as lines, inanother example, probability cones may be shown in place of lines.

In some examples, the system may provide nighttime readiness guidance toprovide a user comfort at night that they will not trend to low glucoselevels at night, to reduce nighttime alerts, and to reduce nighttimehypo events. To develop long range (e.g., 6-10 hours) or high confidencepredictions about states or state transitions, the system retrieve moreinformation from the patient or sensors, or may conduct additionalprocessing, to increase the likelihood that guidance enables a fullnight sleep without interruptions to eat or deliver insulin. Thenighttime readiness feature may provide guidance to take action beforegoing to sleep, e.g. to eat carbs or administer insulin before going tobed.

In some examples, the system may exchange data with a clinicalsupervision platform. The system may provide, receive, or exchangesensor data, patient data, or prescription information or dosinginformation with the clinical supervision platform. In some examples,guidance may be checked against the clinical supervision platform (e.g.,by a human clinician or algorithm) before the guidance is delivered tothe patient. In some examples, guidance, and optionally also resultingdata such as blood sugar curves, may be provided to a clinicalsupervision platform after delivery to the patient, to enablecoordination or feedback from a clinician or otherwise allow for shapingor optimization of future guidance, such as a change of insulin type,dose, or timing.

In some examples, a decision support system may include a diabetescontrol supervisor that may be configured to provide overall guidance orfeedback. The diabetes control supervisor may, for example, overallquantify diabetes control. This may include a metric of effectiveness ofcontrol of estimated blood glucose levels as measured against aspecified condition, criterion, or criteria, such as measure (e.g.,percent) of time within a specified blood glucose range.

Treatment Parameters

A decision support system may also provide guidance regarding treatmentparameters. For example, the system may identify when changes in basalrates, ICR, ISF, or IOB are needed. The system may also prompt for atest, for example if the type or amount of change needed cannot beidentified within a specified metric (e.g., confidence level).Real-world data can present challenges in determining treatmentparameters: Theoretically, if the basal rates are correct and the ISF isknown (or assumed to have a known relationship to other treatmentparameters), a bolus can be determined with acceptable accuracy.Similarly, if the ICR and ISF are assumed to be correct, and carbestimates are assumed to be accurate (at least on average), then thebasal rates may be fine-tuned within acceptable limits. However,real-world conditions may be filled with uncertainty, complexity, andoverlapping factors, and errors can exist in all parameters, which canmake the idealized scenarios described above rare or difficult torecognize. To deal with this systemic complexity, a decision supportsystem may include a model or algorithm may learn or detectinappropriate specific basal rates, ICRs, ISFs, or insulin-on-boardduration from collected data. In some examples, the parameters may bedetermined retrospectively from days or weeks of data and determinedparameters may be evaluated for accuracy as additional data iscollected. A decision support system may also use a model or algorithmand learned parameters or past data in combination with real-time orrecent data to generate guidance, and to calculate a time to deliverguidance.

In an example, in noisy data with multiple overlapping effects, aninappropriate basal rate may be identified by identifying one or morepatterns of recurring lows or highs more than a specified amount of time(e.g., 4 hours) after meals (i.e. after the effects of food and basaldoses have faded). Similarly, an inappropriate ICR may be identified byidentifying recurring low or high glucose levels a specified amount oftime (e.g., 2-4 hours) after meals (while food and basal insulin isstill active) in incidents where recurring lows/highs are did not occurmore than a specified second amount of time (e.g., 4 hours) after thesame meals (which suggests that the basal rate was correct).

The decision support system may account for whether the low or highglucose levels happen with different amounts of carbs, correctionfactors, or initial glucose levels. In an example, if glucose level isin range pre-meal (e.g. no correction bolus on board) but out of rangeafter a meal, then error is likely attributable to an inappropriate ICR.In some examples, glucose trends for meals with differentcharacteristics can be compared to verify or refine detectedinaccuracies in ICR. For example, when a collection of patterns ofglucose levels that trend low reveal that, with a higher carb count, theglucose level trends low faster, or the glucose level gets lower, thenit may be inferred that an ICR is likely too high (i.e. because of thehigh ICR too much insulin is delivered, and the impact of the high ICRis amplified with larger amounts of carbohydrates, which produces fasterlow glucose trends or lower glucose levels.) Similarly, when acollection of patterns of glucose levels that trend high reveals that,with a higher carb count, the glucose level gets high faster or getshigher, it may be inferred that the high glucose trend is likelyattributable to an ICR that is too low (i.e. not enough insulin isdelivered, so glucose levels run high and the impact is amplified withhigher carb counts)

Insulin Sensitivity Factor

In another example, the decision support system may provide guidanceregarding insulin sensitivity. For example, the system may track andreport insulin sensitivity or changes or trends in insulin sensitivity.The decision support system may also provide fault detection (furtherdescribed below) and may assist a user with determining whether aproblem is caused by a treatment parameter or a system fault (e.g., todifferentiate insulin sensitivity problems from hardware faultproblems). Guidance with respect to insulin sensitivity may beparticularly useful when the patient undergoes a change in insulinsensitivity. For example, during “normal” conditions, a patient'sdiabetes may be well controlled, for example by estimating and using“treatment” parameters such as basal rates, ICR, ISF, and insulin timeaction. However, things such as stress, illness, changes in exerciseactivity, and hormone cycles can cause changes in insulin sensitivity,which can change the effects of insulin in the body and may also affectmany or all of the “treatment” parameters (ICR, ISF, etc.), which candrastically affect a patient's glucose levels. In an example, in noisydata with multiple overlapping effects, a decision support system mayidentify an inappropriate ISF based on occurrence of instances of lowsor highs a specified amount of time (e.g., 2-4 hours) after a correctionbolus, in the absence of detected basal errors or detected ICR errors.For example, the system may identify an incorrect ISF from a patternwhere the glucose level is low (or high) after a correction bolus thatis not in response to a meal error. In another example, if a glucoselevel is low (or high) after meals with a correction bolus, and theglucose excursion is not present after meals without a correction bolus,the system may determine that the error is likely attributable to anincorrect ISF.

To detect a change in insulin sensitivity, a decision support system mayuse a model or algorithm capable of identifying changes in glucosepatterns in real time (by using retrospective data). In some examples, adecision support system may use a model or algorithm to distinguishbetween different types of changes in glucose patterns (e.g. insulinsensitivity, insulin delivery problems, sensor problems, etc.). Forchanges in insulin sensitivity, a decision support system may proposeappropriate percentage changes to all “treatment” parameters. The systemmay identify when insulin sensitivity goes back to baseline and proposechanging parameters back to baseline. The system may, for example,distinguish between normal and abnormal states, such as normal ISF andaltered ISF caused by stress, or normal insulin infusion state andabnormal infusion state. In some example, the system may use differentsources of data to detect changes (e.g. sensor glucose readings, sensorraw data, finger-stick data, insulin, carbs, parameter for occlusionalarms in pumps, date of last change of infusion set) and provideguidance based on recognized patterns in the data.

Fault Detection

In addition, system “faults” such as insulin delivery problems (e.g.,infusion site problems) or sensor problems can cause unexpected changesin glucose patterns. A decision support system may identify a faultusing a model or algorithm based on patterns in glucose or other data.Identifying when such fault states begin and end may help a patient andtheir doctor take the appropriate actions to keep glucose levels withinacceptable bounds, and avoid changing other factors (e.g., ISF) in anattempt to address blood glucose excursions when an unrecognized systemfault is driving a glucose control problem.

In some examples, the decision support system may identify instances ofrecurring lows, highs, or out-of-range values that cannot be attributedto ICRs, basal rates, or ISFs with certainty and prompt for basal, ICR,or ISF “tests” to provide additional data with fewer overlapping effectsto enable more accurate deduction of parameter setting problems.

Setting Basal Rates for Insulin Pumps

In some examples, the decision support system may assist with settingand fine-tuning basal rates for insulin pumps. Basal rates may differdrastically throughout the day. For example, a relatively high basalrate may be needed in early morning hours, and a lower basal rate may beneeded in the afternoon. Some insulin pumps allow for setting differentbasal rates every 30 minutes, resulting in 48 possible basal rateparameters per day. The initial setting of these parameters can be verytime consuming, and there may be a lot of uncertainty in the initialdosing. Without appropriate basal rates, it is very difficult toestimate ICR and ISF parameters and retrospectively learn theseparameters. CGM data can be particularly helpful in fine tuning basalrate parameters, because the continuous readings can help identify theexact times when different basal rates are needed. In some examples, asystem may determine basal rate adjustments using patterns in CGM dataor blood glucose levels.

In various examples, a decision support system may combine CGM data withother data to determine or refine bolus rates. For example, a decisionsupport system may assess estimated glucose levels received from a CGMsensor during nighttime, or during periods where other factors are notaffecting glucose levels as determined from sensor or behavioral data,to determine guidance about adjustment of one or more basal rates. Nighttime determinations may be more accurate or more easily determined,because the problem of basal rate adjustment is not complicated by mealsor physical activity. In some examples, a decision support system mayguide a patient through a test protocol to limit the number of variablesthat may affect glucose levels (e.g., limit or regulate exercise,stress, and carbohydrate consumption) to enable accurate determinationof basal rates.

Multiple Daily Injections

In some examples, a decision support system may determine guidance formultiple daily injections of insulin. The body's insulin requirementscan vary significantly during the day. For example, the secretion ofhormones that influence the liver's secretion of glucose (e.g., glucagonsecretions by the pancreas) and the secretion of hormones that increaseinsulin resistance (decrease insulin sensitivity) can generatevariations in insulin requirements. A pattern called the dawnphenomenon, for example, tends to raise insulin levels in the morning.This may be caused, for example, by the secretion of growth hormones orother hormones that cause blood sugar to rise, or by dietaryconsiderations, or by the body's response to a low blood sugar in thenight (Somogyi effect). These effects may be present in any patient, butmay present particularly difficult problems in patients who use multipledaily injections (MDI) of insulin, because the limited number of times aday that insulin can be injected and practical lower-end limits on thesize of a dose that can be delivered.

A decision support system may provide guidance (to a patient orclinician) regarding the size, type, and timing of insulin injections.Patients who use multiple daily injections (MDI) of insulin may use oneor more long or intermediate-acting insulin injections to providebackground insulin around the clock. The timing and dosing ofintermediate or long-acting insulin depends on the onset (how quicklythe insulin begins to act), peak, and duration of action of insulin,which can vary based on the type of insulin and the size of the dose.Long-acting insulins (such as insulin glargine and insulin determir) canprovide a relatively unwavering flow of insulin and consistentabsorption pattern. Intermediate-acting insulins can provide a peak andintermediate duration of action, which can be useful in dealing withpatterns of insulin demand. NPH insulin, for example, is anintermediate-acting insulin that can provide background insulin for upto 24 hours but is much more effective (i.e. more insulin is present inthe blood stream) four to eight hours after injection, and lesseffective 16 to 24 hours after injection.

An intermediate acting insulin such a NPH can be useful in counteringthe dawn phenomenon. Timing the delivery of NPH so that its peak actionmatches the peak basal need is important. In addition, when using anintermediate-acting insulin, it may be important to eat at certain timesor conform to a meal schedule to avoid lows at certain times (e.g., wheninsulin action peaks). The management of glucose levels can be furthercomplicated by the fact that some insulins can have a varied rate ofabsorption from day to day or can produce an unpredictable peak.

Various forms of long-acting insulin or intermediate-acting insulin canbe combined to simulate the body's basal insulin secretion patterns(i.e. if diabetes was not present.) For example, it may be useful tocombine NPH at nighttime and glargine or detemir once daily at a lowerdose to better match the body's basal requirements. However, the amountof insulin coverage provided by medium or long acting insulin orcombinations thereof frequently does not properly match the body's basalinsulin needs, so fine-tuning and careful timing of insulin delivery andmeals can be important. Responding to day-to-day variations can also beimportant.

A decision support system may provide guidance in determining insulindosing and timing to address recognized patterns (e.g., dawnphenomenon). A system may also provide guidance in responding today-to-day variations. For example, a decision support system may detectfrom retrospective data one or more patterns that suggest that amultiple daily injection regimen does not adequately meet a person'sbasal insulin needs. This information may be provided to a patient, ormay be provided to a clinician who may recommend a dosage or regimenchange, or prescribe a different type or brand of insulin. In someexamples, the decision support system may operate as a communicationtool between a patient and clinician to enable the clinician to betterunderstand insulin and glucose patterns (e.g., the system may provideguidance that a patient experiences a low on weekend mornings whenbreakfast tends to be delayed.)

In some examples, a decision support system may provide tools toidentify the mismatch between intermediate and long acting insulinabsorption rates and basal insulin needs. For example, a mismatch may bedetermined from a pattern of high or low glucose levels. In someexamples, the decision support system may account for other factors suchas exercise and food consumption, so that patterns can be identifiedfrom noisy data. In some examples, a decision support system mayidentify recurring events such as hypoglycemia or hyperglycemia causedby inappropriate coverage of basal needs, and provide guidance as topossible solutions (e.g., to eat during a particular time window orconsider changing a dose or injection timing.)

In some examples, a decision support system may identify specificphenomena of interest, such as Dawn phenomenon and Somogyi phenomenon.In some examples, the decision support system may suggest a correctionor suggest inquiry with a physician. For example, Somogyi phenomenon maybe addressed with lowering basal insulin dose, and a dawn phenomenon maybe addressed by using NPH insulin that peaks in the morning or using afast-acting dose of insulin in the morning.

In some examples, a decision support system may identify when basalneeds are not being met appropriately by any combination of MDI therapy.In some examples, the decision support system may provide metrics forbasal therapy success. The decision support system may, for example,evaluate whether steady blood sugar levels are being achieved whilesleeping (e.g., a change of no more than 30 mg/dl assuming whencomplicating factors are not present, e.g., when the patient did noteat, take rapid acting insulin, or exercise a short time before sleep).

A decision support system may also determine when one basal injection isnot sufficient (based on glucose levels and time of injection, and maydetermine guidance to consider (e.g., ask a clinician) an additionalinjection (e.g., inject basal insulin twice a day to achieve a“two-wave” pattern of insulin action) or introduction of another type ofinsulin (e.g., add an intermediate-acting insulin.) The decision supportsystem may include a basal test feature (e.g., an application operableon a smart device), and may identify times when a basal test isnecessary or should be recommended. A basal test may, for example,include a period of relative inactivity and fasting or highlypredictable or controlled eating to reveal underlying basal needs. Insome examples, the system may also determine guidance as to how thebasal requirements can be matched by behaviors, e.g., by combinations ofbasal injections, or injections in combination with meals, or exercise.

Predicting Future Glucose Levels

In some examples, a decision support system may predict blood glucoselevels in advance for a specified time period (e.g., 30 minutes, severalhours, or six hours.) The prediction of blood glucose levels may, forexample, be based upon dietary information (e.g., amount consumed, timeof consumption, carbohydrate and fat or protein content, absorption rate(fast, medium, slow carbs), confidence in food estimate), bolusinformation (time, insulin action, and bolus type (regular ordual-wave), basal rates, exercise, CGM data, blood glucose (e.g., figurestick data), alcohol consumption, stress factors (e.g., based onbehavior or a calendar), or time of day.

The decision support system may predict glucose levels in real-time toprovide advance notice of potential hypoglycemic or hyperglycemic eventsbefore they happen. The predicted glucose levels may, for example, beused to generate an alert or alarm to the user. The predicted glucoselevel may also be used to deliver early guidance to deliver a correctionbolus before a hyperglycemic event occurs or before the patient becomesinsulin resistant due to high glucose levels.

The decision support system may also determine predicted glucose levelsretrospectively or hypothetically to assess treatment parameters ormodel parameters (to assure model parameters are stable). In someexamples, the system may compare predicted values to actual values toassess model parameters.

In some examples, a system may, when confidence in the model is high(e.g., model parameters have been verified or evaluated for accuracy),use a model to test scenarios and predicted outcomes to assess whether apatient or clinician should consider adjusting treatment parameters,such as insulin-to-carb ratio or insulin sensitivity factor. Forexample, the system may run a variety of “tests” on the model, whichwould be burdensome or time consuming for the patient too actually carryout (because of the need to strictly control food, activity, or insulindeliver), and use the results of the tests to determine guidance or atiming of guidance, or to select one or more tests for the patient toactually carry out (e.g., deliver guidance “Your insulin-to-carbohydrateratio may be incorrect: Please conduct a test at your next meal” or“Your basal rate may be incorrect: Please conduct a fasting basal testat your earliest convenience.”) In an example, the system may determinewhat would happen (according to the model) if no meals were ingested: Ifthe predicted blood glucose goes up, a higher basal rate may be needed,and if the predicted blood glucose goes down, a lower basal rate may beneeded. In another example, if the basal rate is assumed to be correct,the system may determine what would happen if a meal is ingested: If thepredicted blood glucose moves back to a target glucose level a specifiedamount of time (e.g. 4 hours) after a meal, the ICR may be deemed to becorrect. If not, the ICR may need adjustment (e.g., a high glucose levelmore than four hours after a meal suggests that the ICR is too low, ifthe underlying basal rate is assumed to be correct). In another example,the system may determine, assuming the basal rate is correct, what wouldhappen if a specified amount (e.g., 1 unit) of insulin were given, andthe system may use this information to suggest an update to an insulinsensitivity factor. In another example, the system may assume a normalabsorption meal and a correct basal rate, and the system may determinewhen the predicted glucose level would reach a steady value, which maybe used to determine a duration of insulin on board. In some examples,the decision support system may use a model to predict recurring low orhigh glucose levels (e.g., using time, based on a pattern observed overtime). In some examples, the decision support system may use a model toidentify Somogyi phenomenon or dawn phenomenon.

Bolus Determinations

A decision support system may develop guidance for delivery of insulinboluses. For example, the system may also include a model or curve-basedcorrection bolus calculator. The system may estimate anindividual-specific post-meals curve, which may for example includecurve estimate parameters such as peak time, peak height dependent oncarbs, and curve “width” based on factors such as the content of themeal and insulin dose and duration. In some examples, the decisionsupport system may first go through a learning period to gather data forestimating curves. The decision support system may use curve estimatesin real time to predict a deviation from a meal curve estimate. Adeviation from a predicted curve may be used to predict and avoidhypoglycemic events, or to predict and treat potential hyperglycemicexcursions. In some examples, two or more estimated curves may becombined to account for overlapping meals. Corrections may also be madeto account for deviations caused by exercise or other factors. In someexamples, similar approaches may be applied to a blood glucoseprediction model, where guidance is based on deviation from a modelinstead of deviation from a curve. For example, a deviation from anoutput expected by model may indicate that an input parameter (e.g.,meal size) was incorrect, and that an appropriate correction (e.g.,re-estimation of meal size or a delivery of a correction bolus) isneeded. The detected deviation may be provided as guidance, oradditionally or alternatively the remedial step (e.g., re-estimation ofmeal size or delivery of a correction bolus) may be suggested asguidance.

Exercise

Exercise can affect blood sugar level quickly (e.g., almostimmediately), and for up to 48 hours after exercise is completed. Adecision support system may provide recommendations on what to do priorto exercising, during exercise, or after exercise. For example, adecision support system may provide guidance with respect to treatmentparameters to account for the effect of exercise. A decision supportsystem may also retrospectively learn and improve exerciserecommendations. In an example, the system may receive from a user(e.g., patient) an exercise plan that may include the type of exercisethat will be performed, the intensity of exercise, and the duration ofexercise, and the system may develop and deliver guidance based on thereceived exercise plan. In an example, the system may provide guidancethat the patient will need a snack of a certain size. When the exerciseis pre-planned (e.g., communicated to the decision support system) atleast an hour in advance, the system may suggest a temporary basal rateto account for the effect of exercise. The system may also suggest apossible temporary basal change if exercise will (or does) last forlonger than one hour. Because exercise can either increase blood glucose(e.g., due to adrenaline secretion which triggers release of glycogen)or decrease blood glucose (due to activity), the system may account forthe type of exercise (e.g., competitive vs. training). In some examples,the effects of exercise may be monitored using CGM or other sensors, anda change in treatment strategy may be learned for each “case” (e.g.intense morning run vs. leisurely afternoon bike ride) to improveguidance and outcomes over time.

In some examples, the system may identify optimal temporary basalpercentage for different types of exercise, intensity, duration, andstart time and deliver guidance that reflects this knowledge. The systemmay also identify optimal meal content (e.g. amount and type of carbs,or fat content) for different types of exercise, intensity, duration,and start time. In some examples, the system may also determine percentactivity adjustment for entry into a bolus calculator.

Example Timelines

FIG. 3A is an illustration of an example timeline 300 associated with apatient. The patient may be engaged in an activity for a period of time,followed by a meal, for which insulin is assumed to have been delivered.After the meal, the patient is available for a period of time, followedby a meeting, and then another period of availability, and then anothermeeting. The decision support engine may take the patient schedule intoaccount in determining when to deliver guidance and what guidance todeliver. For example, through access to the patient's calendar, orthrough learning of the patient's temporal pattern from data, thedecision support engine may be aware of the period of availability afterthe meal and before the meeting, and accordingly deliver guidance duringthis availability period. The guidance may also take into account theupcoming meeting and the length of the meeting and determine guidancethat is calculated to avoid an interruption during the meeting. Forexample, the decision support engine may suggest a large enoughcorrection bolus to control insulin, while managing the risk of a lowglucose level occurring during meeting. In another example, the decisionsupport engine may suggest a pre-meeting snack to sustain glucose levelsthrough the meeting. In some examples, the decision-support engine mayerr on the side of allowing glucose levels to drift low, if it is known(e.g. through a user-supplied preference) that it is easier to consume asmall snack during a meeting than to administer insulin (e.g. if thepatient uses needles or a pen to inject insulin). On the other hand, ifit known that it is easier to administer insulin than consume a snack(e.g. if the user receives insulin through a pump), the guidance may bedetermined to err on the side of a high glucose trend.

FIG. 3B is an illustration of an example schedule of a caregiver (e.g.parent) (top chart) and child patient (lower chart). In an example, thedecision support engine may be aware from calendar information, userinput, sensor information (e.g. GPS), or learned pattern the periods ofavailability of a caregiver, and periods when the caregiver is notpresent or not available. The decision support engine may determineguidance to increase the likelihood of stable glucose levels when thecaregiver is not available. The decision support engine may alsodetermine a time to deliver guidance based on the availability of thecaregiver, e.g. provide guidance early during a period of availabilityduring an early part of a basketball game or defer guidance (whenpossible) to a period of availability at the end of the game.

FIG. 3C is an illustration of a wake/sleep state of a patient. Thedecision support engine may determine a time to deliver guidance whenthe patient is awake, e.g. prior to going to sleep, or during anawakened time during the night, as may be determined, for example, usingactivity or other sensors in a watch, fitness tracker, or other wearableor patient-aware device.

FIG. 3D is an illustration of determination of availability (orconvenience) of a patient to participate in an intervention, based onother states. Initially, the patient is sleeping and not available. Whensleeping ends, the patient is available until a commute begins (asdetermined by schedule information or GPS or connection via to awireless connection in a vehicle). When the commute ends, the patient isavailable until a meeting begins. When the meeting ends, the patientbecomes available again.

Determination of Guidance Timing

FIG. 4 is a schematic representation of guidance determination. Aguidance determination module 402 may receive inputs 404 and determineone or more outputs 404 relating to guidance. The determination module402 may include a model or pattern against which inputs 404 are applied.In some examples, the determination module may include or be a portionof the behavior model. The inputs may be determined by anotherapplication, or state outputs from a model, such as a physiology orbehavior model.

Availability of a user may be received as an input. Availability mayinclude, for example, schedule availability as determined by a calendar,learned or known pattern, user input, or inference. Availability mayinclude actual availability or accessibility (e.g., communicationconnection or type of connection), or user convenience, which may bedetermined or inferred for example, from user activity. Time to nextperiod of availability may also be received as an input, and may bedetermined, for example, from a known, inferred, or user-suppliedschedule or determined pattern of availability. Relatively scarce orinconsistent availability may weigh in favor of determining anddelivering guidance during periods of availability. A short wait untilthe next period of availability may weigh in favor of not deliveringguidance during a present availability window, because anotheravailability window will soon be open. A long wait until the next periodof availability may weigh in favor of delivering guidance during apresent availability window, because if the guidance is not delivered inthe present window, a long wait will be required to deliver guidance, orthe system will need to interrupt the user at an inconvenient time.

Urgency of action may also be received as an input. Urgency of actionmay depend, for example, on the physiological state of the patient orthe nature of the guidance, or both. For example, urgency of action maybe high when a user is rapidly trending toward a low blood glucoselevel, particularly in circumstances when the user may not be aware ofthe trend. Urgency of action may be moderate when a user is slowlytrending toward a low blood glucose level, or when a user is trending ata moderate rate toward a high blood glucose level. Urgency of action maybe relatively low when action is desired, but physiologic risk to thepatient is low. In other examples, urgency of action may be determinedto be high when ingestion of carbs is needed to avoid a low bloodglucose level and may be determined to be moderate when injection ofinsulin is needed, and may be low when testing is needed (e.g. fingerprick blood glucose testing, or temperature or heart rate) to confirm aphysiologic condition or calibrate a sensor (e.g. glucose sensorcalibration.) High urgency of action may weigh in favor of near-termdelivery of guidance, whereas low urgency may weigh in favor of waitinguntil a future period of availability, e.g., to avoid guidance-fatigueor excessive interruption by the user.

The length of a period of an effective action period may also bereceived as input. In an example, it may be determined that ingestion ofcarbohydrates is required within a short period (e.g., a 5-minute periodor 10-minute period). In another example, it may be determined thatinjection of insulin is needed within a moderate period (e.g., a20-minute period). In some examples, the period may be a fuzzy input,e.g., the exact length of the period may not be exact. In some examples,the general size of the action window may be understood, as a reflectionthe variance in action windows for therapeutic or sensor input actions.

Level of concern may also be received as an input. The level of concernof a patient or caregiver may vary amongst patients/caregivers and mayvary depending on the particular situation. Level of concern may, forexample, be determined using patient-supplied information, or learnedfrom data, or received from a model (e.g., a behavior model). High levelof concern by a particular user, or about a particular situation (e.g.combination of physiologic states) may weigh in favor of more near-termdetermination and delivery of guidance, whereas low level of concern mayweigh in favor of deferred determination and delivery of guidance.Engagement may also be received as an input. As described above, levelof engagement may be determined from user responsiveness to alerts orguidance, including for examples the frequency or consistency ofchecking of sensor data (e.g., blood glucose levels), or manner ofengagement (e.g. viewing notification only vs. full data view, or watchvs. smartphone vs. computer). In some examples, a high level ofengagement by a particular user (suggesting concern, availability, orattentiveness) may weigh in favor of more near-term determination anddelivery of guidance, whereas low level of engagement may weigh in favorof deferred determination and delivery of guidance. In other words, tosome extent, the level of availability or concern may be inferred fromengagement. For example, the low level of engagement may result in alower frequency of guidance, for example, so as to avoid overwhelmingthe user. In other examples, a low level of concern by a particularuser, or about a particular situation may weigh in favor of morenear-term determination and delivery of guidance, for example because itmay be determined that the user is likely not aware of a potentialproblem due to the lack of engagement, whereas a high level of concernmay weigh in favor of deferred determination and delivery of guidance,for example because the user may already be aware of a potential problemand highly engaged in monitoring or resolving the problem.

Two or more of the inputs may be used together to determine a time todetermine guidance, a time to deliver guidance, a form of guidance, orcombinations thereof. A time to determine guidance and time to deliverguidance may be related, e.g., the guidance may be determined a shorttime before the time to deliver guidance to assure that the determinedguidance reflects up-to-date real-time data. In an example, the time todetermine guidance may, for example, be deferred when the length ofeffective action period or the time to the next period of availabilityis relatively long, to allow for collection of additional data to refinethe guidance or the accuracy of states from which the guidance isdetermined. In some examples, when a relatively short window ofavailability is open or approaching, guidance may be determined early,even though additional data would normally be desired to get an accurateinterpretation of the physiologic state, to enable delivery of guidance(and time to act upon the guidance) before the window closes. In anotherexample, guidance may be deferred where a time period to a next windowof availability is relatively short. In some examples, the determinationmodule applies weights to the factors to determine whether or when todetermine guidance. In some examples, the determine module determinesprojected future states, or interacts with other modules or models(e.g., the physiologic model) to determine a projected future state andbalance the various inputs against physiologic risks. In some examples,the determination module receives inputs for a number of future times,or determines projected future states, and determines an acceptable oroptimal time or range of time to determine or deliver guidance. Forexample, the module may determine that guidance is not necessary at apresent time (e.g. 4 PM), but that guidance should be delivered at afuture time (e.g. 6-630 PM). In some examples, the module may reassessthe determination as new information becomes available, e.g. as theurgency of action shifts in response to an evolving physiologic state,or as level of engagement changes, or as availability schedule orpattern changes.

FIG. 5A

FIG. 5A is a flowchart that illustrates an example method 500 ofdelivering guidance, such as physiologic glucose concentrationmanagement guidance. The method may provide guidance to facilitatedelivery of therapy such as insulin delivery, carbohydrate ingestion, orphysical exertion to manage glucose levels in a diabetic patient.

At step 502, a real-time datum associated with a patient is measured,determined, or received. The real-time datum may, for example, be areading from a glucose sensor, e.g. a real-time datum received from acontinuous glucose monitoring system that intermittently measures aglucose level and provides the glucose level information through anetwork connection. In an example, it is determined that a user has justeaten a particular meal (e.g. 60 g carbohydrate) for example by mealdetection, user entry, or other pattern detection. In another example,it is determined that a user is about to take their weekly run, asdetermined by pattern recognition of calendar entries. In otherexamples, the real-time datum may also be a time, a deviation from anexpected behavioral pattern, a change of state (e.g. a change ofphysiologic state determined using a model), an indication that amealtime is imminent, a time of day, a characteristic or signaturesignal measured by an accelerometer, a location determined by a GPScircuit, or a request for decision support received through a userinterface. In various examples, the first real-time datum may bemeasured, received, or determined by a smart phone, determined by awearable device such as a watch, or determined by a wearable device incombination with a smart phone. In some examples, the first real-timedatum may be measured, received, or determined by an external device,such as a computer.

At 504, a state the patient is in is determined. The state may bedetermined using a model and the real-time datum, e.g. by applying thereal-time datum to the model.

The model may, for example, include a state indicative of a convenienceor availability of the patient to participate in an intervention. Forexample, information (e.g. availability) from a calendar associated withthe patient, or associated with a caregiver, may be applied to a model.In some examples, sensor information (e.g. accelerometer informationindicating activity level) or pattern information (e.g. indicatingwake/sleep cycles or periods of exercise or periods of transit, e.g.driving) may be applied to a model. A state indicating the availabilityor convenience of performing an intervention such as administeringinsulin or consuming carbohydrates or partaking in physical activity maybe determined by applying the real-time datum to the model. In someexamples, the model may include a patient physiology model, anddetermining a state the patient is in may be based at least on applyingthe first real-time datum to the patient physiology model. In someexamples, the state is an insulin sensitivity. In an example, exerciseis detected, and an insulin sensitivity is determined based upon a knownpattern of user glycemic response to exercise.

The model may additionally or alternatively include a behavior model.The behavior model may, for example, be based on one or moremachine-learned characteristics of the patient. The one or moremachine-learned characteristics may be based on a behavioral orcontextual pattern. In some examples, the behavior model may be based ona set of one or more steps determined to be likely to be performed bythe patient, or one or more objectives determined to be likelyattainable by the patient, or both.

In some examples, the behavior model may include a pattern. In anexample configuration, a patient physiology model is based on aphysiological pattern, and a behavior model is based on a behavioralpattern. In some examples, the first real-time datum may indicate adeviation from an expected behavioral pattern. For example, the firstreal-time datum may indicate a deviation in meal-time, a missed, early,or late insulin dose, a variation in physical activity (e.g. missedworkout or a typical workout), or an early or late awakening. In someexamples, the behavior model may indicate a tendency to over-correct ata meal associated with a meal time, the first real-time datum indicatesthat a mealtime is imminent, and the guidance message may correspond toa lessened overcorrection (e.g. smaller insulin dose or differentcombination of basal and bolus doses) at the mealtime.

In some examples, the behavioral pattern may include a long-termbehavioral pattern based on long-term patterns of behavior and ashort-term behavioral pattern associated with current behavior. Thebehavior model may be based on both long-term behavioral patterns andshort-term behavioral patterns. In some examples, the short-termbehavioral pattern may be based on one or more selected from the groupconsisting of: engagement with mobile device, accelerometer data,frequency of checking glucose concentration, calendar data, andcombinations of these.

In some examples, a determining a state may also be based on ameasurement model. For example, the measurement model may be based on acontinuous glucose concentration monitoring system associated with thepatient. The measurement model may, for example, include an accuracy orother state relating to the glucose measurement. In some examples, themethod 500 may also include measuring glucose concentration datasubsequent to the rendering a guidance message and using the measuredsubsequent data to improve one or more of the models. For example, theglucose concentration data measured subsequent to the rendering may befed back to a measurement model or the behavior model or the patientphysiology model, or to a combination thereof.

At 506, a personalized guidance message may be determined based at leastin part on the determined state. The personalized guidance may, forexample, be a therapy recommendation, such as an instruction toadminister a specified amount (e.g., one unit) of insulin or aninstruction to eat food that contains a specified amount ofcarbohydrates (e.g. five grams of carbohydrates.) In some examples, theguidance message may be based at least in part on a projected transitionto the undesirable physiologic state, such as a high glucose level or alow glucose level. Determining a guidance message may be further basedon a timing of the determining the guidance message or a time associatedwith the determined state. For example, the personalized guidancemessage may be based on timing information obtained from a calendar orpattern or model of an upcoming event. The guidance message determinedat step 504 may provide information to prepare or inform the user forthe upcoming event, such as glucose dosing information or carbohydrateconsumption information, or “Consider dosing with insulin prior to yourupcoming two-hour meeting” or “Consume carbohydrates prior to yourcommute home to avoid a potential low glucose level during yourcommute.” In some examples, the guidance message may be based at leastin part on a determination that a projected transition from a presentstate to a projected state is a low-probability transition. For example,state-transition probabilities may be known or learned from data, andreal-time and other data may indicate that the conditions are presentfor a low-probability transition. This determination may form the basisfor guidance to the patient, and may be particularly useful, for examplein the circumstance where the decision guidance engine may provide analert about risks for which the patient may not be aware.

In some examples, a system detects a state of having missed an exercisesession, or a series of missed exercise sessions, or a trend towardshorter or less intense exercise sessions. Physical exertion by apatient tends to generate increased metabolic drive, which may increaseglucose consumption. A missed or reduced exercise session may result ina lower metabolic drive and a reduced need for calories, or an increasedneed for insulin to compensate for the lower metabolic drive.

The decision guidance engine may also recognize a confluence of factors,e.g. higher-than-normal activity combined with lower than normal foodconsumption, or other patterns such as stress-inducers or lack thereof,travel, sleep disruption, sickness/health, or a typical meal times, anddetermine that a low-probability (given normal condition) statetransition (e.g. from normal too high or low blood glucose levels) mayoccur. Such a determination could lead to determining guidance such as“You may experience an a typical low blood glucose level tonight” or“You may experience an a typical high blood glucose level this morning”or “Your insulin needs may be higher than normal today.” The guidancemay provide details about the reasoning for the guidance (e.g. “ . . .because you missed some workouts”) or may simply notify the user aboutthe physiologic result.

At 508, the guidance message may be provided to the user, such as apatient or caregiver, through a user interface, such as a screen orspeaker of a mobile device, a speaker or display on a vehicle. In someexamples, the manner or time of delivery of the guidance message may bedetermined in part by time (e.g. clock time or time of day), for exampleto account for the patient's work, sleep, dining, or commuting schedule.In an example, providing the guidance message may include displaying thetherapy recommendation at a time calculated to be useful to the user. Inan example, the guidance message may be provided in advance of ascheduled event, such as a meeting. For example, when it is known thatthe user is going into a three-hour meeting, a therapy recommendationmay be given before the meeting, as opposed to waiting for a moreaccurate recommendation to develop or to be determinable. In anotherexample, providing the guidance message may include providing themessage at a time calculated to be useful to the user. For example, whena user is about to go for their usual run, a guidance message with atreatment or monitoring recommendation may be provided before the runstarts, as opposed to when the user trends toward a low blood glucoselevel.

FIG. 5B

FIG. 5B is a flowchart illustration of an example method 501 ofdetermining and rendering a calculated guidance message personalized anduseful to a patient in the therapeutic management of their diabetes, ata time calculated to be useful to the patient. The examples discussed inreference to FIG. 5A may also be applied to the method of FIG. 5B.

At 501, the method may include measuring, determining, or receiving afirst real-time datum associated with the patient. The first real-timedatum may, for example, be a glucose concentration value, a time of day,meal information, a request for advice received through a user interface(e.g. via a smartphone app), activity information (e.g. from a fitnesstracker or watch, or insulin delivery information, which may be receivedvia a user interface or from a smart device such as a pen or pump.

At 503, the method may include, using a model, determining a state thepatient is in. For example, the determining may be based on a patientphysiology model, a behavioral model, and a measurement model. The statemay be determined by applying the real-time datum to the patientphysiology model and the behavioral model. The patient physiology modelmay, for example, be a state model that includes one or more of aglucose concentration state, an insulin-on-board state, an insulinsensitivity state, an energy absorption state, or an energy exertionstate. A particular state may be determined by features of availableinput (e.g. time of day, glucose level, prior activity.)

At 505, the method may include determining a guidance message. Theguidance message may be personalized to the patient based on at leastthe determined state.

At 507, the method may include providing the determined personalizedguidance message via a user interface, such that the rendering occurs ata time calculated to be useful to the patient in the therapeuticmanagement of their diabetes. Providing the determined personalizedguidance message may include rendering the personalized guidance messageon a user interface.

The method may also include learning the model from a set of input data.The set of input data may include a clock time, a time of day, glucoseconcentration levels, insulin on board, patient activity, patientwellness, day of week, day of month, day of year, location, foodconsumed, or beverage consumed, and information received through a userinterface. Other input data are also possible, including for example theinformation described with respect to FIGS. 2B and 14-16.

The learning of the model may occur before, or after, the receiving ofthe real-time datum. For example, the method may further includedetermining a deviation from an expected state after delivering thepersonalized guidance message, and adapting the model based onadditional input information.

FIG. 6

FIG. 6 is a flowchart that illustrates an example method 600 ofdetermining and rendering a calculated guidance message personalized anduseful to a patient in the therapeutic management of their diabetes. Atstep 602, the method 600 may include receiving data relating to apatient, the data including a real-time glucose concentration level. Thereal-time glucose concentration level may be received, for example, froma glucose sensor, such as a continuous glucose monitoring system.

At 604, a patient state may be determined by applying the data to astate model. The patient state may, for example, be a physiologic state,such as any one of the physiologic states described above. For example,the state may include an insulin state, such as an insulin on boardstate, an insulin sensitivity state, an insulin action time state, or acombination thereof. The state model may also include a behavioral orcontextual state or a measurement state. The state model may, forexample be a probabilistic state model. The state model may includestate transition probabilities that are learned from retrospective data.In some examples, the model includes a multitude of sources, and isinformed using retrospective data, or data captured in real time. Themodel may also include probabilities, such as the probability of statetransitions, or combinations of state transitions. In some examples, astate or number of states may be determined based upon CGM data andother input data to determine a patient state. In other words, thesystem may work backwards through the model to determine whatcombination of parameters is most likely to provide a current CGM valueof X. This combination of parameters (e.g. states) may be considered“the state the patient is in.”

At 606, a therapy recommendation based on the determined state may beprovided. The therapy recommendation may include, for example, guidanceregarding delivery of insulin, consumption of carbohydrates, protein,fat, or other nourishment or other food or drink. The therapyrecommendation may be delivered to the patient or a caregiver, e.g. viaan electronic communication delivered through a visual user interface(e.g. screen), speaker, or other communication mechanism. The method mayfurther include refining the state model using data received afterdelivery of the therapy recommendation. For example, physiologic data orstate changes may be entered into the model, and the model may learnfrom the actual data and refine the model based on input conditions andactual outputs. The system may also refine the determination ofparticular states, or refine the determination of guidance, in view ofthe physiologic results of prior guidance.

FIG. 7

FIG. 7 is a flowchart illustration of a method 700 of determining anddelivering a calculated guidance message that may be personalized anduseful to a patient in therapeutic management of their diabetes.

The method may include at 702 learning a personalized behavior model ofthe patient. The learning may, for example, be based on a preexistingdata set, data captured in real-time, or a combination thereof. Learningthe model may include learning both the physiology of the patient, andthe behavior of the patient, both of which may be characterized asstates. Learning the personalized behavior model of a patient mayinclude machine learning one or more characteristics of the patient,such as a physiological pattern, a contextual pattern, or a behavioralpattern, or a combination of these patterns.

The method may also include, at 704, receiving a real-time datum. Thereal-time datum may include any of the examples describe herein, such asa CGM sensor datum, location, network connection, or physiologic sensordatum.

The method may also include, at 706, determining a personalized guidancemessage to be rendered to the patient. The determining of thepersonalized guidance message may be based at least in part on the timeof determination of the personalized guidance message and thepersonalized behavior model of the patient. The method may also include,at 708, determining a delivery time to provide the personalized guidancemessage using the learned personalized behavior model, wherein thedelivery time is calculated to be useful to the patient in thetherapeutic management of his or her diabetes. The method may alsoinclude delivering the personalized guidance message at the deliverytime.

FIG. 8

FIG. 8 is a flowchart illustration of an example method 800 of providingdecision support functionality for a user. The method may include, at802, loading a model into a memory of a computing environment. Themethod may also include, at 804, receiving a datum indicative of aglucose concentration value of the user. The method may also include, at806, causing a display of a calculated insight on a user interface ofthe computing environment. The insight may for example be calculatedusing at least the model and the datum indicative of the glucoseconcentration value. In some examples, a user request may trigger thecausing of display of the calculated insight. The user request may, forexample, be associated with data entry of a planned activity. Thecalculated insight may indicate a user act calculated by one or more ofthe models to result in a desired outcome associated with the glucoseconcentration value, such as maintaining the glucose concentration level(or a rate of change thereof) in a target range, or above or below acertain level. The planned activity may, for example, be a meal, and thecalculated insight may be a calculated or predicted effect of the mealon the glucose concentration value, or a strategy (e.g., insulindelivery or activity or both) to manage glucose concentration levelsafter the meal. In some examples, the calculated insight may include aninteractive recommendation and at least one factor used in determiningthe interactive recommendation.

In some examples, the causing a display of the insight may be initiatedby an occurrence of an event that matches a predetermined condition,such as a blood glucose level or trend, or an arrival at a destinationas determined by a GPS system, or an event inferred from a pattern ordetermined using calendar information.

In some examples, the causing a display of the guidance may be initiatedby an occurrence of an event that matches a calculated condition. Thecalculated condition may be calculated based at least in part on themodel, or the datum indicative of the glucose concentration value, or acombination thereof. For example, when a therapy adjustment exposes theuser to more risk than was present before the therapy adjustment, alertsand/or alarms may be adjusted to have additional sensitivity for aperiod of time following the therapy adjustment. In another example,detecting when a time period exists following a potential treatmentdecision that triggers a more frequent instantiation of a CGM app thanprior to the potential treatment decision may lead to the messagingfrequency of a decision support application being increased.

FIG. 9

FIG. 9 is a flowchart illustration of a method 900 of deliveringphysiologic glucose concentration management guidance. At step 902, themethod may include receiving a datum indicative of a glucoseconcentration level. At step 904, the method may include determining astate by applying the datum to a model. At step 906, the method mayinclude determining a guidance message based on the state and a temporalpattern. The temporal pattern may include, for example, a learnedtemporal pattern or a user-defined schedule (e.g. calendar of thepatient or a caregiver). The pattern may include a pattern of one ormore states correlated to time, or typical blood glucose concentrationlevels, ranges, or patterns correlated to time or events.

FIG. 10

FIG. 10 is a flowchart illustration of a method 1000 of deliveringphysiologic glucose concentration management guidance. The method 1000may include, at step 1002, receiving a datum indicative of a glucoseconcentration. At step 1004, the method may include determining apatient state by applying the datum to a model.

At step 1006, the method may include determining whether the patientstate is a typical. Determining whether the patient state is a typicalmay include determining whether the patient state is a typical for agiven set of conditions, determining whether a low-likelihood statetransition has occurred, determining whether a low-likelihood statetransition is projected to occur. In an example, determining a patientstate includes determining a physiological state and a behavioral state,and determining whether the physiological state is a typical for thedetermined behavioral state. In further examples, determining whetherthe patient state is a typical includes identifying a blood glucoseconcentration level that deviates from a controlled blood glucoseconcentration range a time or in a circumstance when blood glucoseconcentration is typically in a controlled range, identifying a bloodglucose concentration trend leading to a high or low blood glucoseconcentration state a time or in a circumstance when blood glucoseconcentration is typically in a controlled range, or includesanticipating a shift to a low blood glucose concentration state at atime or in a circumstance when blood glucose concentration is typicallywell controlled.

At step 1008, the method may include determining a guidance messagebased on the atypicality of the patient state; and at step 1010,delivering the guidance message through a user interface.

FIG. 11

FIG. 11 is a flowchart illustration of a method 1100 of deliveringphysiologic glucose concentration management guidance. The method mayinclude receiving a datum indicative of a glucose concentration,determining a patient state by applying the datum to a model,determining from the model that a low-probability state transition hasoccurred or is likely to occur, and delivering through a user interfacea guidance message based on the determination that the low-probabilitystate transition has occurred or is likely to occur. For example, apattern may be recognized for which, under general conditions, thetransition to a particular state is a low probability, but underspecific conditions as indicated by real-time data or user input, apattern is recognized for which the transition is actually likely. Forexample, the method may include alerting a user that an a typical stateis likely, when glucose levels are normally controlled at that time. Forexample, the user may be alerted of an anticipated low glucose levelfollowing exercise. Exercise can lead to a low glucose level severalhours after the exercise is completed (e.g., due to increased insulinsensitivity or restoration of glycogen reserves). The user may bealerted of the possibility or likelihood of such a “late low.” The alertmay be delivered or prioritized if the low is calculated to occur atduring sleep or at an inconvenient time. In some examples, the alert maybe delivered at a time that is calculated to be useful to the user, suchas at time before the patient is expected to go to sleep, to avoidwaking the patient or a caregiver.

FIG. 12

FIG. 12 is a flowchart illustrating a method 1200 of deliveringphysiologic glucose concentration management guidance. The method mayinclude, at 1202, receiving a datum indicative of a glucoseconcentration, at 1204, receiving one or more behavioral, environmentalor contextual inputs, at 1206, identifying a likely transition to anundesirable patient state by applying the datum and the one or morebehavioral, environmental or contextual input to a model, at 1208,determining a guidance message based on the likely transition to anundesirable patient state; and at 1210, delivering the guidance message,wherein the guidance message is determined and delivered at a time suchthat the patient can intervene to avoid the transition to an undesirablepatient state.

FIG. 13

FIG. 13 is a flowchart illustration of a method 1300 of deliveringphysiologic glucose concentration management. The method may include, at1302, receiving a datum indicative of a glucose concentration, at 1304,determining a physiologic state using the datum, at 1306, determining abehavioral state, at 1308, determining a guidance message based on thephysiologic state and the behavioral state, and, at 1310, delivering theguidance message using a user interface. Example Inputs and Outputs—FIG.14-16

The flowchart 650 of FIG. 14 indicates ways of quantifying non-crispinputs. In particular, upon reception of a non-crisp input (step 219),one way of quantifying the same is performing a step of natural languageprocessing (step 221) on the input to determine a “crisp” equivalent.For example, if the user indicates qualitatively that they consumed aglass of orange juice, natural language processing may determine howmany carbs are involved in a glass of orange juice, thus translating theinput from non-crisp to crisp. Historical pattern data may also beemployed in this regard. Similar such natural language processing may beemployed to determine the crisp nutritional content of an input such as“I had a quarter pounder at McDonald's”. Social networks and socialmedia may also be employed (step 223) to give context to non-crispinputs or to otherwise tighten down values pertaining to non-crispinputs. Big data may also be employed (step 225) to give context andcrisp values to non-crisp inputs. For example, population data may beemployed to determine what a particular user means by a particularphrase or indication of a parameter, e.g., by analysis of cohort data,and the same may be employed along with any of the other techniques torender a crisp version of the input that will result in (step 227)quantifiable criteria that may be employed to influencedecision-support.

Particular and other aspects of inputs are described below in the Inputssection.

However, prior to a general discussion of inputs, and referring to FIG.15, particular types of relationships are shown, and a particularrelationship is shown by the relationship 231 between a food sensitivity233 d and a meal bolus 235 a. Other relationships may also be determinedusing systems and methods according to present principles, betweeninputs 233 a-233 e (only a sampling of such inputs is shown) and variousoutcomes or in particular outputs 235 a-235 e (again, only a sampling ofsuch outputs are shown). Processing steps 237 are indicated to show howthe correlative parameter, e.g., food sensitivity 233 d, is used alongwith a real-time input (not shown) within the processing steps 237 toresult in a therapy recommendation of a meal bolus 235 a. Particularexamples of these inputs and outputs are described below in the Examplessection.

The identification of the correlative parameter and thelifestyle/situational parameter, as well as subsequent processing steps,can be performed in a number of ways. For example, the steps can includefactors from various locations, including social networks, user-entereddata, sensor data, data from user devices, population or big data, andso on. The processing and identification may include Bayesian analysisor the like, e.g., to identify strong connectors which are parameters orvariables that bear a strong relationship to each other. Where multipleparameters are employed, the same may include multiple parametersrelating to the same event, e.g., both intensity and duration ofexercise. The processing and identification may include multiple steps,e.g., a first step of processing “internal data” for that patient, and asubsequent step of performing some processing in the cloud, with “big”data, e.g., using prepackaged subroutines and case-based reasoning. Forexample, case-based reasoning may be employed to determine what happenedto the user in other like situations, or what happened to other likeusers in other like situations. As smart devices become even morecomputationally capable, much of the machine learning may happen on suchdevices. However, much of the current processing can happen in thecloud, and such processing may result in significant amounts of machinelearning. In other words, the system learns how one element or“affector” X affects the patient, e.g., how anabolic exercise may impactinsulin sensitivity. In this example, if a pump action was initiatedwith the bolus but did not consider the impact of exercise, and then theuser goes for a run, systems and methods according to present principlesmay detect this sequence of events and notify the user to “expect adrop” or may provide a recommendation such as “you should eat somethingnow”.

As noted above, a final step in this method is modifying the input oroutput interface based on the identified correlative parameter or stateas well as on a real-time input. The real-time input may include alifestyle or behavioral or situational parameter, e.g., a time of day,an event about to be undertaken as determined by a clock or calendarapplication or user input, glucose value, and so on. In other words, themachine/human interface is modified by the decision-supportapplication/functionality, e.g., on the smart device, smart phone, smartwatch, and/or as part of the input user interface or output userinterface of any of these devices, based on the results of the abovesteps. For example, the output user interface, i.e., the type, format,and content of the output, may then depend on the lifestyle/situationalcontext as well as on the parameterized model and/or the user-definedfunctionality. It should be noted that a specific user-definedfunctionality, e.g., a lifestyle goal, need not be employed in everyimplementation, although such may be advantageously used to guidecertain therapy recommendations.

In modifying the machine human interface, just as inputs may becategorized or “fuzzified”, outputs may be provided in categories or“fuzzifications” as well, and such is particularly true if the output issimply to be rendered on a user interface of a display. For example, ifthe therapy recommendation is to suggest that a user have a large glassof orange juice, or eat a medium apple, the user may find such arecommendation more useful than a recommendation to eat a certain amountof carbohydrates. Of course, if the output includes an output to a pumpor pen, no such “fuzzification” is necessary and as much accuracy aspossible is generally desired.

FIG. 15—Outputs

Exemplary outputs are as illustrated in FIG. 15, e.g., a recommendationof a type, amount, and timing of a meal bolus 235 a, a recommendation ofa type, amount, and timing of a correction bolus 235 b, a recommendationof a type, amount, and timing of a meal 235 c, a change in the userinterface 235 d, e.g., providing an alert or an alarm at a timedetermined to be effective for user, or a pre-event or situationaldecision 235 e, e.g., a decision to be made before sleep, a meal,exercise, driving, activity, or the like. Other exemplary outputsinclude a permanent or temporary change to a basal rate setting, arecommendation for rescue carbs, or the like. Specific outputs, and theway the same may change according to the decision-supportapplication/functionality, are discussed in the Outputs section below.

While various core methods have been described above with regard toproviding decision-support application/functionality in a way that issupportive of user-defined functionality, it will be understood that thecore methods need not be mutually exclusive. For example, variouscombinations of the core methods may be employed in a givenimplementation. In addition, multiple methods may be performed inparallel to determine optimal treatment decisions, and then the safestoption chosen. That is, various algorithms may be employed as describedabove to use defined states, sensor data, user inputs, and otheravailable information to calculate an optimal diabetes treatmentdecision. Multiple methods may be performed in parallel to calculate theoptimal treatment decision, and then the most conservative or safest ofthe solutions may be provided to the user. For example, in times ofsensor noise, either a filtered value or the raw sensor value may beused to calculate a current glucose estimate and subsequently arecommended insulin bolus. Doses could be calculated based on bothsensor values in parallel and then the more conservative dose could berecommended. Another example is to use a glucose rate of change estimatebased on either a trend calculated in the CGM algorithm or as atwo-point difference of the most recent pair of glucose values, and therate of change that provides the more conservative dose would be used.

A number of exemplary inputs and notations about such inputs are givenin the table. It will be understood that other inputs may also beemployed, and that the notations given about the inputs are notnecessarily limiting. For example, inputs may be noted as having acertain context, but in some cases the context may be thought of asoverlapping certain categories. As another example of variations,certain inputs may be identified as user entered, but in some cases thesame may be determined by a sensor or the like. For example, meal datamay be determined by user input, but also by GPS, from pattern data orfrom an app such as a camera. As noted the decision-supportapplication/functionality incorporates machine learning to increase theaccuracy and appropriateness of therapy prompts over time. Meal dataentered by the user, e.g., “small meal”, “medium meal”, and so on, maybe “learned” by the system so that the decision-supportapplication/functionality may better understand over time what the userconsiders a “small meal”, and so on. Temporal patterns may be analyzedby the systems and methods to determine aspects of, e.g., meals andexercise; but users may also identify and quantify events they want totrack, including those corresponding to meals and exercise.

In one alternative implementation, the algorithm may have just one“average” meal defined but allow for a degree of automatic adjustment todefine what is large or small for a user. In this implementation, the“average” meal may be defined for a population or for an individualuser. This implementation may be more convenient to implement as onlyone meal size need be defined, and the same does not need to be changedfor every meal. Rather, a multiplier may be applied, by the patient, bythe HCP, or automatically, to assess if the meal is “average”, “light”,or “heavy/large”. The algorithm may then automatically increase ordecrease suggested insulin amounts according to the assessment. Forexample, an exemplary “multiplier” may be that a large meal is 1.5× theeffect of the “average” meal, or that a small meal is 0.5 times theeffect of the “average” meal. Such implementations may be particularlyconvenient for a user to implement, particularly where the user is notaccustomed to carb counting. Extensions of such an idea to exercise andother applications will be understood.

Where multiple types of data are employed as inputs in a givenalgorithm, the multiple types may be related, e.g., may be a type,timing, and intensity of a variable, e.g., illness, exercise, meals,sleep, and so on, e.g., a duration and intensity of exercise.

In the table the inputs are divided into two categories: real-time dataand non-real-time data. Referring also to FIG. 17, these categories ofinputs 246 are then divided into subcategories as: data from sensors(248 and 252), user data 254 which may be user-entered data or data fromother apps, e.g., from a suitable API, derived data, and other data.Some subcategories appear in both real-time data and non-real-time data.In any case, the inputs 246 then feed into a user device 256 which maybe a dedicated receiver or smart phone, and more particularly into adecision-support application 260 disposed therein. Derived data 262 maybe stored in the user device 256, and a display 258 may be provided witha user interface to display prompts to the user as well as for receivinguser-entered data. The derived data 262 may be derived by a processorwithin the user device 256, and the derivation of the data may occurwithin the decision-support application/functionality or may occuroutside of the same.

FIG. 16—Inputs

Referring back to the types of data illustrated in FIG. 16, the subsubcategories then describe specific types of data or are themselvescategories. For example, a sub subcategory in real-time data is“physiological sensors” and these may be further broken into differenttypes, e.g., CGM, SMBG sensors, body temperature sensors, skinconductivity sensors, hormone sensors, heart rate sensors, and the like.Besides physiological sensors, other sensor data includenon-physiological sensors, such as those dealing with atmosphericpressure, accelerometers, GPS, sensors measuring aspects of the CGMsystem itself, temperature sensors, and the like. Such inputs may beprovided from wearable devices/sensors, e.g., those available from anApple Watch®, Fitbit®, or other wearable. Other devices providing inputsmay include other mobile devices, including smart phones.

Sensors such as accelerometers and GPS may be conveniently used toprovide data about exercise or activity performed by the user. In somecases, GPS or other sensors may be employed to determine other types ofactivity data, e.g., if a user is driving, which may in turn inform howan output to a user may be displayed, e.g., on a smart watch versus on asmart phone.

In the particular case of an accelerometer, the same may beadvantageously employed to detect sleep patterns or sleep quality asrelated to glucose control. Such may generally provide data related toposition but also importantly to activity detection as well as durationand intensity. One potential type of accelerometer that may beadvantageously employed is a three-axis accelerometer.

In some cases, the decision-support application/functionality may allowdata to be entered about the start (or other marker) of a menstrualcycle. In this way, users may be able to track over several months thebehavior of blood sugar at different times of the month with regard tothe cycle. Of course, such an algorithm and data may also be used on itsown to assist pregnancy efforts or if using the rhythm method for birthcontrol.

Hormone sensors may provide another source of entered data, and in oneexample may also be a source of data related to the menstrual cycle.Other hormone sensors may include those that sense cortisone and/orepinephrine. Hormone sensors or the like may also be employed to providea measure of “energy in” versus “energy out”, particularly with regardto a parameterized system model of the patient.

Another subcategory of inputs in real-time data includes user-entereddata, including goals, a problem to be solved, a desire for therapy,entered data about stress, emotion, or feelings, pain level data, sleeplevel data, data from a follower device, pump data, meal data, exercisedata, blood glucose data from an external blood glucose meter, and soon. User-entered data may include user estimates of glucose values, sothat decision-support may be rendered in a way that helps the user tobetter correlate a perceived glucose value with a real one. For example,the decision-support application/functionality may be enabled to betterassist the user in determining and discerning what different levels ofhyperglycemia feel like. User-entered data may also include userdemographic data such as age, gender, and so on. Such data may beconveniently obtained by, e.g., a swiping of the user's driver'slicense.

Where user-entered data includes exercise, systems and methods accordingto present principles may allow users to save specific workouts orevents to allow patterns in post workout glycemic fluctuations to beanalyzed and potentially found, resulting in appropriate automatic ormanual therapy modifications to be made by the decision-supportapplication/functionality. For example, users may save workouts such as“Cardio 1”, “Cardio 2”, “Get Swoll 1”, “Get Swoll 2”, and so on. Othergradations of exercise may include those pertaining to intensity, e.g.,light, medium, hard, duration, e.g., 5 min., 10 min., 15 min., 20 min.,25 min., 30 min., one hour, and so on.

Goal data may include an indication of priorities in terms of glucosecontrol, e.g., hypoglycemic versus hyperglycemic avoidance. Differentcontrol types may be provided as preprogrammed profiles that a user maychoose in selecting a goal. For example, a user may choose a goal ofhypo-minimizing control, hyper minimizing control, frequent versusinfrequent correction boluses, and so on, so as to fit differenttreatment styles and goals.

In the same way, user feedback may also constitute an important inputinto decision-support. That is, the decision-supportapplication/functionality may be modified based on user feedback, e.g.,periodically querying the user as to what they would like to bedifferent about their recent glycemic control and providing options suchas “I would like to reduce my number of nighttime hypos” or “I wouldprefer to not have to give correction boluses as often”. Feedback may beprompted for in a convenient fashion to minimize annoyance for the user.For example, feedback may be provided by slider bars or other userinterface elements convenient for user selection. Slider bars may alsobe provided for other user inputs, e.g., to indicate how muchinteraction is desired.

As noted above the decision-support application/functionality may beadvantageously employed as part of a bolus calculator. Thus, user inputmay also include user input into such a bolus calculator. For example,the decision-support application/functionality may be rendered with auser interface that affords the user predetermined dose adjustments,e.g., +/−0%, +/−10%, +/−20%, and so on. The dose adjustments presentedmay themselves depend on the CGM trend, e.g., negative dose adjustmentsmay be provided in the case of a negative or falling glucose trend. Thechosen adjustment would apply to the bolus dose calculated with orwithout any other trend adjustment. Alternatively, adjustments can befuzzy. In yet another implementation, users can choose to customize theadjustment, within bounds. Over time, with data, the decision-supportapplication/functionality may determine optimal adjustments based onthis user-entered data (and other inputs), and with providerauthorization (or alternatively without providerauthorization/confirmation), the adjustment options may be presented tothe user and re-determined.

In a related implementation, rather than a percentage, rate of changedata may be employed to increase/decrease the bolus value calculated bya fixed amount. In this way, the patient adds or subtracts enoughinsulin to cover that amount of glucose change from their meal bolususing their own insulin sensitivity/correction factor. In thisimplementation, initially the bolus calculation could be leftunmodified, and the decision-support application/functionality may learnhow much insulin needs to be added or subtracted based on rate of changeas part of a case-based learning process. For example, in cases whereglucose is rising or falling, rather than updating insulin sensitivity,the system may learn how far the glucose is from target and considerthat to be the amount of glucose that should be accounted for. In thiscase a new insulin sensitivity is not learned, but rather the bestinsulin sensitivity estimate is used based on the other descriptors ofthe case, e.g., lifestyle factors, e.g., specific to an insulinsensitivity for breakfast with no exercise. As it may be desired tolearn both how much to adjust insulin boluses based on rate of changeand how insulin sensitivity changes for time of day, exercise, etc.,systems and methods according to present principles may advantageouslyseparate the two problems and only update insulin sensitivity when ratesof change are relatively stable. Once it is learned how much the usershould adjust their insulin based on rate of change, then such data maybe pushed to the HCP, e.g., showing patterns of, e.g., how the userpost-meal glucose is always around 30 mg/dL too high when they take ameal bolus and the trend arrow is 90 degrees up, and the HCP may berequested to approve the amount of insulin to add or subtract. Machinelearning may also be used to determine if it is better to modify insulinboluses based on rate of change using a percent or a fixed amount, justin case such may vary patient-to-patient. Additional details of the useof rates of change data are provided below in an example.

Returning to the discussion of various inputs, inputs may include dataabout followers of the user, or data about other related users. Thisentered data may include data about social groupings, e.g., for theachievement of individual or group goals, and may further employ naturallanguage processing to deduce objective and quantifiable desires andgoals of the group or its members. Inputs may further include inputsfrom followers, e.g., in response to a query such as “What do you thinkis going on with your daughter?”.

Another source of real-time data that is user entered includes mealdata. Users may enter meal data in a fuzzy or categorized fashion oralso as a crisp input. Machine learning may be employed to learn in anobjective sense how a user categorizes the meal. For example, if a userterms a meal “small”, in terms of what is entered into thedecision-support application/functionality, the system may learn in amore quantitative or objective way what the user considers a “small”meal. The same is true for meals entered and termed as other sizes. Thesame is also true for user-entered data regarding meal composition. Inother words, the system can learn what a user means when the user entersa statement of meal composition into the decision-supportapplication/functionality. For example, if the user terms a meal “highcarb”, the system can learn from the glucose response and data aboutdelivered insulin (if available), in combination with the meal data,what the user considers “high carb”.

Another subcategory of inputs in real-time data includes data from otherapplications or “apps”, e.g., generally from a suitable API. Such appsmay reside on the computing environment providing the decision-supportapplication/functionality or may be in wired or wireless communicationtherewith. Such apps include: calendar apps, GPS apps, CGM apps, appsholding historical data or other information, SMBG apps, temperaturemonitor apps, Healthkit®, data from followers, e.g., from text messagingapps, bolus calculator apps, clock apps to provide time of day, appsindicating the elapsed time, so as to allow user prompts to be providedat optimum times, apps providing access to cloud data or “big” data,camera apps, pump applications, pen applications, bolus calculatorapplications, and the like. As a particular example, a texting or emailapp may refer to an event, e.g., a dinner party. Through an appropriateAPI, the texting or email app may then serve as a source for input ofcalendar data. In a specific example, there could be an option for “addevent to CGM” or the CGM (or equivalently decision-supportapplication/functionality) could automatically pull event data whenevera calendar event is added. Such facility would allow users to createcalendar events and CGM events at the same time, providing an easier wayto collect event data and see how events affect glucose trends.

For example, bolus calculator decision-support generally requires entryof meal data. In one implementation, a camera application may prompt theuser to take a picture of a meal on a plate (see FIG. 18A). The user mayuse the phone camera to take the picture, and brackets may be providedas part of a user interface on the screen to guide the user on how totake the picture. The app may then measure the meal size in relation tothe plate size and denote the meal as, e.g., small, medium, or large.The app may then give a dose recommendation based on the meal size. In amore enhanced implementation, the app may use photographic recognitiontechniques to determine, estimate, or guess what is on the plate, andprovide an estimate as to the consequent meal composition. Variationswill be understood. For example, in an alternative implementation, theuser prompt may instruct the user to swipe through different circle (orother shape) sizes over a picture of the meal on the plate (see FIG.18B). They app may then ask the user to find the circle size that bestmatches the meal size on the plate.

Other real-time data that may be provided from an app includes pump orrelated data, including recent boluses, basal rate, and the like. Asanother example, the prompt may be provided based on estimatedinsulin-on-board in conjunction with CGM inputs and other contextualinformation. Insulin-on-board is a term used to describe the amount ofinsulin that has been given to the patient but that has not been used bythe body to transport glucose into the tissue. If after taking a mealbolus, the estimated insulin-on-board is still one half of the originaldose, but measured glucose has already dropped to 80, an alert might beprovided because continued insulin activity is expected, furtherlowering the glucose to hypoglycemic levels.

In more detail, patients who administer too much insulin are at risk ofhypoglycemia and possible death. There are currently no real-timemeasurement methods to measure how much insulin is within the patient.Insulin stacking occurs when an insulin using patient administersmultiple boluses of insulin within a short timeframe. Insulin from theprevious dose may not have taken its full effect and therefore thepatient may give themselves too much insulin on subsequent doses, posinga significant danger of hypoglycemia to the patients. A continuousdirect insulin sensor may be employed to measure the amount of insulinthat is within a patient. This detector can be used as an alert or as afailsafe to shut off a pump or an artificial pancreas. As each patientgenerally has a different insulin sensitivity (but this sensitivity maybe learned using the decision-support application/functionalitydescribed here), multiple thresholds are generally needed for alertsettings.

A secondary aspect to this implementation includes the use of a directinsulin sensor to monitor how much insulin is in the patient. The amountof insulin can be used to give the patient feedback to recommend a safedose of insulin. The insulin information can also be transmitteddirectly to a calculator or pump and used in an insulin dosingcalculation to better estimate the proper amount of insulin to dose.This could be used instead of the current insulin-on-board estimationused in bolus calculators.

A third aspect of this implementation describes the use of a directinsulin sensor to measure a patient's insulin sensitivity. Insulinsensitivity can vary between patients and even over time with the samepatient. Accordingly, systems and methods according to presentprinciples may use a direct insulin detector to measure the amount ofinsulin in a patient's body. By combining the information of glucose andinsulin concentration within a patient into an algorithm, the insulinsensitivity can be calculated. The information contained in the insulinsensitivity can then be used to determine if an insulin sensitizer,insulin secretagogue, or insulin, should be used to manage the diabetes,e.g., to increase or decrease the amount of insulin that the patient isgiven to best control their glucose levels.

Returning to the chart of inputs of FIG. 16, and as another example ofreal-time data, which may also be used in non-real-time, GPS data froman app or other such sensor may be employed for a user away from home,e.g., for a user at college, to determine potential followers orfriends.

Calendar apps may be employed to provide data about users. As an exampleof determining data from multiple different sources, exercise data maybe determined from calendar data, if the exercise is located within anappointment notation or if a pattern of exercise implies that a userexercises at the same time every day or week.

As another example of inputs, safety rules may be employed to providedecision-support to various levels of aggressiveness. For example, if auser does not provide detailed meal information, then a decision-supportapplication/functionality which is providing a user prompt to drive theuser's glucose level to a target range may aim for the high end of thetarget range rather than the middle of the target. In the same way, ifthe user provides meal data indicating a very large amount ofcarbohydrates, then the high-end of the target range may again be aimedfor in the decision-support application/functionality, as errors in carbcounting are known to have worse effects as the overall carb amountincreases.

As another example of inputs, device diagnostics may serve as an input,including device signal quality and confidence, as well as to determinerisk stratifications based on the same. For example, meal or correctionboluses or other decision-support prompts may be informed at least inpart by confidence intervals, and the confidence intervals may beinformed at least in part by device signal quality and/or detectedfaults.

Cloud or big data may also be used. As an example of the use of cloud orbig data, a HCP may desire to determine initial values for insulinresistance or insulin sensitivity. The HCP may enter demographic datasuch as weight, age, and gender. The app may then search through adatabase and find users most similar to the subject user, and may takean average of their settings for initial suggestions. Cloud or big datamay further be employed for initial risk stratification, again based onaggregate numbers.

As noted above, a CGM app may provide an input to the decision-supportapplication/functionality. For example, in some implementations it maybe preferable to handle glucose levels outside of a range of, e.g.,40—400, using fuzzy logic. Yet other data which may serve as an inputand which is available from a CGM app may include a target glucose levelor range.

Yet another type of input involves derived data. Derived data, whichalso may also in some cases constitute real-time data, includes ananalyte rate of change or acceleration, various types of sensitivities,including sensitivities to insulin, sleep, meal, and/or exercise, ahierarchy within a risk stratification (described in greater detailbelow), glucose variability, user stress/emotions/feeling data, a userdesire for interaction with the device, sensoraccuracy/confidence/signal quality, pattern data, and the like. Suchsensitivities often constitute lifestyle factors as defined above. Theabove-noted detection of hormone levels may further aid in the detectionand quantification of insulin sensitivity, as hormone levels are knownto be an associated factor.

Insulin sensitivity can be based on sleep, energy intake versus energyoutput, food intake, and the like. Insulin sensitivity can changerapidly and with, e.g., circadian rhythms. Insulin sensitivity is knownto be event driven, stress driven, and also driven by factors such asillness, activity, or the like. If a user employs a CGM monitor, eventsaffecting insulin sensitivity can be detected, and a measure of insulinsensitivity may even be determined from knowledge of intake values ofcarbohydrates into glucose and basal/bolus amounts of insulin. Typicaland a typical ranges of insulin sensitivity can also be determined.Insulin sensitivity can be measured by, e.g., measuring a basal rate atthe same time each day, and seeing how glucose values change withrespect to various events including meals, exercise, stress, or thelike, and further by performing the same test with various changes inbasal rate. Insulin sensitivity may also be detected by testing levelsof various hormones, including cortisol and/or epinephrine.

Derived data corresponding to meal sensitivities may be made even moregranular by determination of, e.g., sugar sensitivity, dinnersensitivity, and so on. Other such perturbation or interactionsensitivities will also be understood to be derivable.

“Insulin-to-carb” ratios may also constitute derived data, and the sameare generally determined and optimized using retrospective analysis. Thesame may be used to provide decision-support education for a user bydemonstrating graphically the impact of different insulin-to-carblevels. In particular, with knowledge of insulin delivery, thedecision-support application/functionality, or a related or connectedmodule, may display to the user the effect of using differentinsulin-to-carb ratios on their glucose levels, e.g., by modifying aretrospective glucose trend line. Within the decision-supportapplication/functionality, optimal insulin-to-carb ratio settings couldbe automatically determined, and it may be further determined howinsulin-to-carb settings vary with time of day, activity level, or thelike.

In some cases, derived data requires a time duration over which toanalyze or an analysis of a pattern to determine. For example, adetermination of insulin sensitivity or an insulin resistance mayrequire analysis of data taken over a time duration. In a specificimplementation, insulin resistance can change throughout the menstrualcycle of a female diabetic patient. The decision-supportapplication/functionality can use a resulting cycle of insulinresistance, e.g., including incorporating insulin consumption as well asglucose values, to determine a predictive insulin resistance alert toprovide to the user. For example, the patient could receive a reminderat the beginning of the day that historically in their cycle their bloodsugar tends to go higher or lower. Such a prompt made help the patientbe more conscientious of how they could expect their blood sugar tobehave.

For an initial or seed value of insulin sensitivity, population data maybe employed from a database of patients, particularly those of similarweight, age, gender, length of diabetes, and so on. Such may be used fordefault values and then auto adjusted as additional information aboutthe user becomes known over time.

Meal data may also be a form of derived data as the same may be derivedfrom food patterns, food libraries, and so on. In another way ofderiving meal data, retrospective analytics may be employed to use otherdata to estimate carb content for a given meal. Such other data mayinclude, e.g., insulin delivered, glucose levels, exercise, health, mealtime, and the like. By collecting such data, the decision-supportapplication/functionality may be enabled to determine a user's typicalmeal and typical glucose response to that meal while mitigating theeffect of other factors on their glucose. Such functionality has severalbenefits, including improving accuracy of bolus calculators, the abilityto optimize alerts if the system notices an a typical glucose response,assistance to users in understanding their eating patterns and theeffects of different meals on their glucose, and more accuratecalculation of insulin to carb ratios.

Derived data may further include user estimation data, e.g., whether andby how much a user is apt to make an error in carb counting, e.g., tooverestimate or underestimate.

Derived data may also include data determined about recognized patterns,where the patterns are recognized by analysis of historical data overtime. Exemplary recognized patterns include patterns of nightlyhypoglycemia, postprandial highs, post exercise lows, or the like.

One way of determining such patterns, or of detecting occurrences ofglucose events not in patterns, is by “binning” certain events definedby particular characteristics. That is, portions of glucose traces maybe detected that meet predefined criteria indicative of certain diabeticchallenges, e.g., rebound hypoglycemia, and then patterns may be lookedfor in these events that have been “binned” accordingly.

FIG. 19 Et Seq.

In more detail, and referring to the flowchart of FIG. 19, a signatureor fingerprint in glucose sensor data may be identified ordifferentiated within an individual patient based on some predefinedcriteria (step 262). Such criteria may include time-based criteriaand/or may include detected specific incidents within specificconstraints. In the present system, according to present principles,bins may be differentiated by different criteria. A supervised learningalgorithm may be employed that allows for more bins to be learned forindividual specific patterns. For example, bins can be based on insulindata, rate of change of glucose data (or acceleration/decelerationthereof), patterns of data identified before and used to characterizedata, e.g., events occurring before small meals, responsiveness of anindividual to their glucose information, and so on.

A next step is that the incident may be characterized, e.g., based on adecay curve, waveform signature, or the like (step 264). Exemplaryincidents may include meal bolus indicators, e.g., based on insulindata, which may be classified into small, medium, and large meal bins.Such may correlate with insulin data. Different meal types may also becharacterized, which may then be sub-binned into different mealcompositions. These may correlate with rate ofchange/acceleration/deceleration. Incidents can also be characterizedbased on their correlation with events before a meal, and suchcorresponds to the patterns of data noted above. Incidents may furtherbe based on behavioral patterns, e.g., how often a user reviews theirglucose data or responds to alarms, and such can be correlated with theresponsiveness data noted above. It will be understood that other binsmay also be employed.

The characterized incidents may then be placed into a bin (step 266). Bythen synchronizing by incident, bins may be tuned for specific patientphysiology. The bins can then be normalized, i.e., a normal distributionof incidents in the bin may be defined (step 268).

The normalized bin information may then be used proactively as an inputinto the decision-support application/functionality (step 268), e.g., inthe determination or definition of the state according to Step A. As oneexample, the normalized bin information may be an input to a boluscalculator. The normalized bin information may also be employed torespond to other requests proactively determined or requested by theuser, e.g., when a user asks for a bolus calculation before a meal, orwhen the system prompts for a bolus calculation before a meal based ontime or other factors. The binning technique may be employed todetermine when a patient is more tuned into their data, based onbehavioral input, which may then allow for more aggressiverecommendations as opposed to the case when the user is not focused onglucose information, e.g., nighttime, when the bolus recommendation isgenerally more conservative.

Returning to FIG. 16, in non-real-time data, inputs may includeuser-entered data such as prior SMBG data, user savviness withtechnology, goal data, a problem to be solved, a certain desire for thetherapy, a target glucose level, demographic data such as age andgender, their cardio health, cholesterol level, a type of mathematicalcalculation to be employed (typically entered by default or by a HCP),data about illness or pregnancy or menstruation, data about medicationstaken, smoking history, and the like. Non-real-time data may alsoinclude derived data, including historical patterns, gastric emptyingduration, or the like. Other non-real-time data may include data about afollower, e.g., their tone of communications, their language, and so on.These may be employed in modifying outputs for greater effectiveness tothe user.

With regard to gastric emptying duration, it is noted that 25% of thediabetic population (type 1 and type 2) experience some form of gastricemptying delay. 7 to 12% of the same group suffers from an elevateddelay for gastric emptying. The population of gastric emptying delay isincreasing at a very significant rate within the diabetic population,and is becoming a concern for health care professionals within thegeneral population currently.

Current bolus wizards do not factor in gastric emptying, thus certainrisks exist. For example, if gastric emptying is not factored into aclosed loop pancreas system, the individual runs the risk of glucosevariability where there are repeated corrections and insulin deliveryreductions. This results in chaotic insulin delivery which wouldresemble a successive approximation wave form over time. If the same isnot used within a bolus calculator for an insulin pump, the result is toendanger the person as they may suffer a hypoglycemic event which wouldroughly correlate to the size of the meal which they had dosed for. Theymay also suffer a hyperglycemic event which would roughly correlateagain to the meal size, as its effects would take effect when thereactance of the insulin is reduced and is declining within the system.

Over time such variabilities can manifest themselves into further damagewhich may degrade gastric function over time. Additionally, the personruns the risk of increased peripheral neuropathy.

Gastric emptying delays push out the process of moving processed andprepared nutrients and food into the small intestines where actualabsorption of nutrients occurs and can be triggered by such factors asneuropathy of the vagus nerve, nerve damage within the stomach, andmuscle damage within the stomach. Gastric emptying studies are used byGI doctors to quantify the extent of the delay which may result in aprognosis of gastro paresis.

The general direction given to insulin dependent diabetic patients is todose (bolus) between 0 and 30 minutes prior to a meal. The rational inthis directive is to time the effect of the insulin to correspond to thetime at which the consumed food enters the absorption phase. This timingis accurate in the case where gastric emptying is not an issue (75% ofthe type 1 & type 2 population). However, in the balance of thepopulation, the delivery time of the insulin is inaccurate. Fast actinginsulin reaches maximum effectiveness roughly 90 to 120 minutes after abolus is delivered. This is the delay from bolus delivery, propagationthrough the body and adherence to the A & B receptors on the surface ofthe cells. At that time, the cells are able to process sugars and do so.However, for an individual with a gastric emptying delay, the deliveryof the processed foods to the system has not occurred yet. For theseindividuals, roughly 90 to 120 minutes after eating (if they dosed abolus 30 minutes prior to a meal) they will suffer a hypoglycemic event.This event is generally addressed with a liquid such as orange juicewhich enters the intestines and system more quickly than solid food.

The insulin reaction is on the decline at the end of the peak for anelevated case of gastric emptying delay at the time where the food isbeing processed and is entering the system. This results in ahyperglycemic event at which a correction bolus needs to be delivered.Thus, gastric emptying duration may be employed as an input in order toprovide a time delay for delivery of a bolus after a meal. This delaymay be applied to a bolus calculator or to a closed loop artificialpancreas system. Gastric emptying duration may also be employed as aninput in order to provide a time delay for a modified basal rate after ameal. This delay may be applied to an insulin pump or to a closed loopartificial pancreas system.

One way of determining gastric emptying delay within an individual is asfollows. If a CGM user enters a bolus and a meal, then the following 4hours of data are analyzed within the CGM. If there is a repeatableevent which occurs for the individual which follows a trend, then agastric emptying delay may be inferred. The inferred delay may then beapplied to the bolus and/or modified basal rates as described above.

Referring to the example shown in FIG. 20, time period (a) indicatesbolus and food entries. They are also offset from one another. Timeperiod (b) indicates the period when food processing should occur,however, for this exemplary patient, the food processing is delayed.Time period (c) indicates when food should be processed normally as itwould align with the bolus. Time period (d) indicates when actual foodprocessing occurs in a gastric delay. The slope of the BG decline isindicative of the rate of gastric emptying delay as well as the generaldelay. This delay is also represented within the BG value signal bydetermining the deltas between the start of (c) & (d) as well as theirdurations. In order to isolate this signal within the general noisewithin the blood glucose signal, insulin sensitivity is calculated fromthe individual's blood glucose data.

Referring again back to FIG. 16, non real-time data may further includestored data, as stored and retrieved from memory or other storage.Stored data may include historical data, both of determined patterns anddata used for determining patterns or other glucose events. Stored datamay include prior user events. For example, if a HCP has previouslycommented on a pattern, if the pattern repeats, the HCP comment may bere-displayed on the user interface.

Inputs can be “fuzzy”, e.g., may fall into certain categories, and thecategories themselves used as inputs, e.g., small/medium/large meals, or“less than normal”/normal/“more than normal”, or alternatively theinputs may be crisp. Thus, also shown in the table are exemplarycategorized or fuzzy inputs, as well as exemplary crisp inputs. Thetable also indicates an interpretation as to the type of context for theinput, e.g., whether the same concerns lifestyle aspects, situationalaspects, clinical aspects, or device aspects. In some cases, an inputmay occupy more than one category.

The way in which inputs are used and aggregated may vary. In oneimplementation, a function may be determined, or a user system model maybe created, and the inputs used directly on the function or model. Inanother example, in a hierarchical approach, the decision-supportapplication/functionality may be designed to use information obtainedfrom different sources in a layered approach. Bare-bones systems willuse CGM data, and as additional data is received, the same may be usedfor decision support. The confidence in estimates and decisions thengenerally improves as the amount of information increases. In the sameway, users or use conditions may be categorized in buckets or layers ofrisk. Each time information is available, the system may move up or downthe hierarchy in order to ensure safety.

In addition, as may be understood from the above, combinations of inputsmay themselves result in an additional input. For example, analternative empirical approach may be to control aggressiveness based onhistorical levels or success of predictions. For example, aggressivenessin decision-support may be reduced when the situation, e.g., time ofday, day of week, type of event, and so on, has historically resulted invariable or poorly-predicted glucose levels. For example, a user mayconsume a very consistent lunch during the week and inconsistent luncheson weekends, where the consistency refers to timing, meal size, and mealcontent. The inconsistency may result in less predictable results ofpre-lunch boluses on weekends. The decision-support applicationfunctionality may then detect this poor predictability and adjustaggressiveness accordingly.

Referring to FIG. 21, modes of operation of the CGM app ordecision-support application/functionality may serve as inputs which inturn may be categorized in different ways. For example, the mode ofoperation may refer to a calibration mode, such as deviceself-calibration or factory calibration. The mode of operation may alsorefer to a transmission mode (transmission of data to a display device),such as scheduled transmissions or unscheduled transmissions. It will benoted that all of these modes described are exemplary and that othermodes of operation are also possible. The mode of operation may alsorefer to a decision-support mode, such as therapeutic, non-therapeutic,adjunctive, non-adjunctive, and so on. As may be seen in the figure,even where the modes may be thought of as being operationallysequential, the decision-support application/functionality may jump fromone mode to an adjacent mode or from one mode to a nonadjacent mode. Anexample is the case of scheduled transmissions, where in mode 1 atransmission is made every 30 seconds, in mode 2 a transmission everyminute, in mode 3 a transmission every 5 minutes, and so on. In manycases such modes will not be marked by just a change in a characteristictime, but rather by a change in functionality, e.g., from periodic toaperiodic.

Signals may be collected from sensors within smart watches such as theApple Watch and the Microsoft Band to augment certain entered data,e.g., for hypoglycemia detection. The signals can include heart rate,sympathetic/parasympathetic balance (inferred from heart rate),perspiration, motion, and the like. The signals can be used in additionto the CGM signal. Algorithms employed to process the auxiliary signalscan be trained on the patient's own data, using CGM to assist in thetraining. These outer limits can be optimized off-line, or in the cloud.Detection criteria then can be sent to the patient's smart phone and/orsmart watch. For example, there may be instances when CGM fails todetect hypoglycemia, but when augmented with auxiliary signalsindicating possible hypoglycemia, the patient may be alerted tosuspected hypoglycemia and thereby enabled to avoid the consequences.Alternatively, after the algorithms used to process the auxiliarysignals have been trained, the smart watch signals can be used to detecthypoglycemia without the use of CGM. In this use case, adjustments tothe algorithms may be used to optimize sensitivity/specificity.

Detected cognitive ability may also serve as an input. In more detail,it is noted that cognitive ability and motor function may be affected bynumerous varied inputs and effects. For example, an individual withdiabetes may suffer from reduced cognition and/or motor functions as afunction of hypoglycemia. As a hypoglycemic incident occurs, and bloodsugar levels drop, the individual suffers from concentration and/orcomprehension degradation. Additionally, due to the body responding to alack of sugar, the muscles may tense and begin to act erratically.

With a capacitive ability on an input device, such as a smart phone ortablet, the user may view information, makes decisions, and press onscreen indicators to perform device interaction. As a user becomesfamiliar with an application on such a device, their ability to makedecisions increases, while the delay between interactions reduces. Theyadditionally develop a series of familiar sequences in order to performcommon tasks that they have become accustomed to.

However, when an individual suffers from a drug interaction, alcohol, orhypo/hyper glycaemia, these familiar tasks become less familiar. Thisresults in a situation where the user must spend more time observing andcomprehending a user interface which normally is intuitive and requiresno concentration. The time spent on a user interface screen willlengthen compared to the historical norm of the individual. When themotor functions of a user degrades due to any of the mentionedinfluences, the ability to press an on screen indicator such as abutton, a slider, or onscreen keyboard, become less uniform, and maydeviate from the normal metrics for the user. In such situations, theinitial press location in relation to the center point of the controlmay deviate from the user's normal press location. Additionally, where apress/lift action is the interaction to a button, in a motor controldeficient situation, the press may be followed by a “drag” motion, andthe lift location of the interaction may change. By accumulating themetrics of time and user interaction on a user interface screen, e.g.,the press XY location for a control in relation to its center point, theXY distance travel prior to lifting the finger, the duration of pressedstate, and the like, a profile of the user's interaction can bemaintained. This data can then be correlated to the user blood sugarreading in order to determine a general population behavior, as well assub populations based on gender, age, and so on. This information canfurther be used to determine where the cognitive ability/motor functionability of an individual rests, in relation to population groups towhich the individual is a part of. A degree of impairment for aparticular individual may also be determined and used as an input. Inother words, the decision-support application/functionality may makedecisions and/or actions based on this information, e.g., by using thesame in the definition of a state according to Step A. Such decisionsand actions may be to alert another individual in order to notify orrequest assistance. It may also be used to disallow operation of a motorvehicle or other potentially unsafe action in such a condition.

In a related implementation, a guiding “wizard” component mayinstantiate if the cognitive ability is degraded. In this case, moreverification may occur such as “You are about to change your settings,are you sure you want to do this?”, safety guidance such as “you shouldwait until your blood sugar rises before changing your sensor” mayoccur, and so on.

In another implementation, once motor function degradation is detected,buttons and user interface components can be enlarged, or a larger pressarea may be utilized. It also may interpret a “drag” motion on a buttonas a “press” action, thus assisting the individual.

In this way, patients affected by hypo/hyper glycaemia may be assisted,and their followers notified of their condition. It may further keepthose impaired by alcohol from trying to take unsafe or untimelyactions. It may further identify anecdotally if a drug interaction ordrug reaction is occurring. It may further track such data over time inorder to accrue reaction over time to such events. It may generate datauseful in determining a person's condition in relation to a populationof similar people.

Another type of data which may be employed in providing decision-supportis diabetic subtype. In particular, diabetes is currently categorizedinto two different categories. Type I diabetic patients are unable toproduce insulin and thus rely on an external source of the same. Type IIdiabetic patients have a nonoptimal insulin production capability andgenerally rely on injected insulin in order to offset the physiologicalinsulin production anomaly. Various subtypes of these may also beunderstood, generally corresponding to genetic mutation. Geneticmutation #1 involves a marker within the genetic sequence of individualswhich results in a surfaced apology aberration on the sales of thesubject. This aberration causes a reduced ability for insulin to adhereto the A and B receptors on the cell surface. The effect of theinhibition or reduced adherence results in a difficulty for insulin toperform its effect. This causes insulin to take a longer period of timeto adhere to cellular surfaces, thereby reducing the effect of a knownvolume of insulin. Additionally, a longer period of time is required inorder for the insulin to adhere to an adequate population of cells inorder to cause a measurable effect on blood glucose levels. This isreferred to as insulin resistance. Genetic mutation #2 is the oppositeof genetic mutation #1, and results in a surfaced apology deviation inindividuals which allows for easier than normal adherence of insulin,resulting in a quicker cellular response as well as a larger populationof cells responding to the insulin. By dividing patients by subtype ofdiabetes, additional personalization and tuning/tailoring of therapyprompts may be provided.

Another type of user-entered input which may be employed in thedecision-support application/functionality is user input on alertthresholds so as to reduce alert batik. User-entered thresholds mayreduce the number of clicks necessary for the user to set up alerts. Inthis implementation, and referring to FIGS. 22A and 22B, a user can, onthe user interface, touch the actual threshold line on the graph anddrag it to the alert threshold they desire. A pop-up value informs theuser of the current exact value of the threshold. When the user takestheir finger off the line, a pop-up will ask the user if the thresholdis correct. This functionality mitigates accidental touch and drag. In avariation, the graph could be one allowing the user to follow dailytrends and set alerts corresponding to their daily activities.

The above description has included various types of inputs. Other andmore examples of inputs, and the use of the same in decision support,are described below with regard to specific examples. Examples are alsoprovided in which variables are tied together to glean other andadditional data, e.g., if GPS indicates very rapid movement, it may beinferred that the user is driving and this information used indecision-support. In addition, other examples of determining inputs, andin more detail the use of smart phones to glean lifestyle information,are disclosed in co-pending U.S. patent application Ser. No. 13/801,445,file Mar. 13, 2013, entitled “Systems and Methods for LeveragingSmartphone Features in Continuous Glucose Monitoring”, owned by theassignee of the present application and herein incorporated by referencein its entirety.

System Details

FIG. 23 depicts in further detail elements of the example system 100, inaccordance with some example implementations. The system 100 may includea continuous analyte sensor system 8 including sensor electronics 12 anda continuous analyte sensor 10. The system 100 may include other devicesand/or sensors, such as medicament delivery pump 2 and glucose meter 4.The continuous analyte sensor 10 may be physically connected to sensorelectronics 12 and may be integral with (e.g., non-releasably attachedto) or releasably attachable to the continuous analyte sensor 10. Thesensor electronics 12, medicament delivery pump 2, and/or glucose meter4 may couple with one or more devices, such as display devices 14, 16,18, and/or 20.

In some example implementations, the system 100 may include acloud-based analyte processor 490 configured to analyze analyte data(and/or other patient-related data) provided via network 406 (e.g., viawired, wireless, or a combination thereof) from sensor system 8 andother devices, such as display devices 14-20 and the like, associatedwith the host (also referred to as a patient) and generate reportsproviding high-level information, such as statistics, regarding themeasured analyte over a certain time frame. A full discussion of using acloud-based analyte processing system may be found in U.S. PatentPublication No. US-2013-0325352-A1, entitled “Cloud-Based Processing ofAnalyte Data” and filed on Mar. 7, 2013, herein incorporated byreference in its entirety. In some implementations, one or more steps ofthe factory calibration algorithm can be performed in the cloud.

In some example implementations, the sensor electronics 12 may includeelectronic circuitry associated with measuring and processing datagenerated by the continuous analyte sensor 10. This generated continuousanalyte sensor data may also include algorithms, which can be used toprocess and calibrate the continuous analyte sensor data, although thesealgorithms may be provided in other ways as well. The sensor electronics12 may include hardware, firmware, software, or a combination thereof,to provide measurement of levels of the analyte via a continuous analytesensor, such as a continuous glucose sensor. An example implementationof the sensor electronics 12 is described further below with respect toFIG. 24.

In one implementation, the factory calibration algorithms describedherein may be performed by the sensor electronics.

The sensor electronics 12 may, as noted, couple (e.g., wirelessly andthe like) with one or more devices, such as display devices 14, 16, 18,and/or 20. The display devices 14, 16, 18, and/or 20 may be configuredfor presenting information (and/or alarming), such as sensor informationtransmitted by the sensor electronics 12 for display at the displaydevices 14, 16, 18, and/or 20.

The display devices may include a relatively small, key fob-like displaydevice 14, a relatively large, hand-held display device 16, a cellularphone 18 (e.g., a smart phone, a tablet, and the like), a computer 20,and/or any other user equipment configured to at least presentinformation (e.g., medicament delivery information, discreteself-monitoring glucose readings, heart rate monitor, caloric intakemonitor, and the like).

In one implementation, the factory calibration algorithms describedherein may be performed at least in part by the display devices.

In some example implementations, the relatively small, key fob-likedisplay device 14 may comprise a wrist watch, a belt, a necklace, apendent, a piece of jewelry, an adhesive patch, a pager, a key fob, aplastic card (e.g., credit card), an identification (ID) card, and/orthe like. This small display device 14 may include a relatively smalldisplay (e.g., smaller than the large display device 16) and may beconfigured to display certain types of displayable sensor information,such as a numerical value, and an arrow, or a color code.

In some example implementations, the relatively large, hand-held displaydevice 16 may comprise a hand-held receiver device, a palm-top computer,and/or the like. This large display device may include a relativelylarger display (e.g., larger than the small display device 14) and maybe configured to display information, such as a graphical representationof the continuous sensor data including current and historic sensor dataoutput by sensor system 8.

In some example implementations, the continuous analyte sensor 10comprises a sensor for detecting and/or measuring analytes, and thecontinuous analyte sensor 10 may be configured to continuously detectand/or measure analytes as a non-invasive device, a subcutaneous device,a transdermal device, and/or an intravascular device. In some exampleimplementations, the continuous analyte sensor 10 may analyze aplurality of intermittent blood samples, although other analytes may beused as well.

In some example implementations, the continuous analyte sensor 10 maycomprise a glucose sensor configured to measure glucose in the blood orinterstitial fluid using one or more measurement techniques, such asenzymatic, chemical, physical, electrochemical, spectrophotometric,polarimetric, calorimetric, iontophoretic, radiometric, immunochemical,and the like. In implementations in which the continuous analyte sensor10 includes a glucose sensor, the glucose sensor may comprise any devicecapable of measuring the concentration of glucose and may use a varietyof techniques to measure glucose including invasive, minimally invasive,and non-invasive sensing techniques (e.g., fluorescence monitoring), toprovide data, such as a data stream, indicative of the concentration ofglucose in a host. The data stream may be sensor data (raw and/orfiltered), which may be converted into a calibrated data stream used toprovide a value of glucose to a host, such as a user, a patient, or acaretaker (e.g., a parent, a relative, a guardian, a teacher, a doctor,a nurse, or any other individual that has an interest in the wellbeingof the host). Moreover, the continuous analyte sensor 10 may beimplanted as at least one of the following types of sensors: animplantable glucose sensor, a transcutaneous glucose sensor, implantedin a host vessel or extracorporeally, a subcutaneous sensor, arefillable subcutaneous sensor, an intravascular sensor.

Although the disclosure herein refers to some implementations thatinclude a continuous analyte sensor 10 comprising a glucose sensor, thecontinuous analyte sensor 10 may comprise other types of analyte sensorsas well. Moreover, although some implementations refer to the glucosesensor as an implantable glucose sensor, other types of devices capableof detecting a concentration of glucose and providing an output signalrepresentative of glucose concentration may be used as well.Furthermore, although the description herein refers to glucose as theanalyte being measured, processed, and the like, other analytes may beused as well including, for example, ketone bodies (e.g., acetone,acetoacetic acid and beta hydroxybutyric acid, lactate, etc.), glucagon,acetyl-CoA, triglycerides, fatty acids, intermediaries in the citricacid cycle, choline, insulin, cortisol, testosterone, and the like.

FIG. 24 depicts an example of sensor electronics 12, in accordance withsome example implementations. The sensor electronics 12 may includesensor electronics that are configured to process sensor information,such as sensor data, and generate transformed sensor data anddisplayable sensor information, e.g., via a processor module. Forexample, the processor module may transform sensor data into one or moreof the following: filtered sensor data (e.g., one or more filteredanalyte concentration values), raw sensor data, calibrated sensor data(e.g., one or more calibrated analyte concentration values), rate ofchange information, trend information, rate of acceleration/decelerationinformation, sensor diagnostic information, location information,alarm/alert information, calibration information such as may bedetermined by calibration algorithms, smoothing and/or filteringalgorithms of sensor data, and/or the like.

In some embodiments, a processor module 214 is configured to achieve asubstantial portion, if not all, of the data processing, including dataprocessing pertaining to factory calibration. Processor module 214 maybe integral to sensor electronics 12 and/or may be located remotely,such as in one or more of devices 14, 16, 18, and/or 20 and/or cloud490. In some embodiments, processor module 214 may comprise a pluralityof smaller subcomponents or submodules. For example, processor module214 may include an alert module (not shown) or prediction module (notshown), or any other suitable module that may be utilized to efficientlyprocess data. When processor module 214 is made up of a plurality ofsubmodules, the submodules may be located within processor module 214,including within the sensor electronics 12 or other associated devices(e.g., 14, 16, 18, 20 and/or 490). For example, in some embodiments,processor module 214 may be located at least partially within acloud-based analyte processor 490 or elsewhere in network 406.

In some example implementations, the processor module 214 may beconfigured to calibrate the sensor data, and the data storage memory 220may store the calibrated sensor data points as transformed sensor data.Moreover, the processor module 214 may be configured, in some exampleimplementations, to wirelessly receive calibration information from adisplay device, such as devices 14, 16, 18, and/or 20, to enablecalibration of the sensor data from sensor 12. Furthermore, theprocessor module 214 may be configured to perform additional algorithmicprocessing on the sensor data (e.g., calibrated and/or filtered dataand/or other sensor information), and the data storage memory 220 may beconfigured to store the transformed sensor data and/or sensor diagnosticinformation associated with the algorithms. The processor module 214 mayfurther be configured to store and use calibration informationdetermined from a calibration.

In some example implementations, the sensor electronics 12 may comprisean application-specific integrated circuit (ASIC) 205 coupled to a userinterface 222. The ASIC 205 may further include a potentiostat 210, atelemetry module 232 for transmitting data from the sensor electronics12 to one or more devices, such as devices 14, 16, 18, and/or 20, and/orother components for signal processing and data storage (e.g., processormodule 214 and data storage memory 220). Although FIG. 24 depicts ASIC205, other types of circuitry may be used as well, including fieldprogrammable gate arrays (FPGA), one or more microprocessors configuredto provide some (if not all of) the processing performed by the sensorelectronics 12, analog circuitry, digital circuitry, or a combinationthereof.

In the example depicted in FIG. 24, through a first input port 211 forsensor data the potentiostat 210 is coupled to a continuous analytesensor 10, such as a glucose sensor to generate sensor data from theanalyte. The potentiostat 210 may also provide via data line 212 avoltage to the continuous analyte sensor 10 to bias the sensor formeasurement of a value (e.g., a current and the like) indicative of theanalyte concentration in a host (also referred to as the analog portionof the sensor). The potentiostat 210 may have one or more channelsdepending on the number of working electrodes at the continuous analytesensor 10.

In some example implementations, the potentiostat 210 may include aresistor that translates a current value from the sensor 10 into avoltage value, while in some example implementations, acurrent-to-frequency converter (not shown) may also be configured tointegrate continuously a measured current value from the sensor 10using, for example, a charge-counting device. In some exampleimplementations, an analog-to-digital converter (not shown) may digitizethe analog signal from the sensor 10 into so-called “counts” to allowprocessing by the processor module 214. The resulting counts may bedirectly related to the current measured by the potentiostat 210, whichmay be directly related to an analyte level, such as a glucose level, inthe host.

The telemetry module 232 may be operably connected to processor module214 and may provide the hardware, firmware, and/or software that enablewireless communication between the sensor electronics 12 and one or moreother devices, such as display devices, processors, network accessdevices, and the like. A variety of wireless radio technologies that canbe implemented in the telemetry module 232 include Bluetooth, BluetoothLow-Energy, ANT, ANT+, ZigBee, IEEE 802.11, IEEE 802.16, cellular radioaccess technologies, radio frequency (RF), infrared (IR), paging networkcommunication, magnetic induction, satellite data communication, spreadspectrum communication, frequency hopping communication, near fieldcommunications, and/or the like. In some example implementations, thetelemetry module 232 comprises a Bluetooth chip, although Bluetoothtechnology may also be implemented in a combination of the telemetrymodule 232 and the processor module 214.

The processor module 214 may control the processing performed by thesensor electronics 12. For example, the processor module 214 may beconfigured to process data (e.g., counts), from the sensor, filter thedata, calibrate the data, perform fail-safe checking, and/or the like.

In some example implementations, the processor module 214 may comprise adigital filter, such as for example an infinite impulse response (IIR)or a finite impulse response (FIR) filter. This digital filter maysmooth a raw data stream received from sensor 10. Generally, digitalfilters are programmed to filter data sampled at a predetermined timeinterval (also referred to as a sample rate). In some exampleimplementations, such as when the potentiostat 210 is configured tomeasure the analyte (e.g., glucose and/or the like) at discrete timeintervals, these time intervals determine the sampling rate of thedigital filter. In some example implementations, the potentiostat 210may be configured to measure continuously the analyte, for example,using a current-to-frequency converter. In these current-to-frequencyconverter implementations, the processor module 214 may be programmed torequest, at predetermined time intervals (acquisition time), digitalvalues from the integrator of the current-to-frequency converter. Thesedigital values obtained by the processor module 214 from the integratormay be averaged over the acquisition time due to the continuity of thecurrent measurement. As such, the acquisition time may be determined bythe sampling rate of the digital filter.

The processor module 214 may further include a data generator (notshown) configured to generate data packages for transmission to devices,such as the display devices 14, 16, 18, and/or 20. Furthermore, theprocessor module 214 may generate data packets for transmission to theseoutside sources via telemetry module 232. In some exampleimplementations, the data packages may, as noted, be customizable foreach display device, and/or may include any available data, such as atime stamp, displayable sensor information, transformed sensor data, anidentifier code for the sensor and/or sensor electronics 12, raw data,filtered data, calibrated data, rate of change information, trendinformation, error detection or correction, and/or the like.

The processor module 214 may also include a program memory 216 and othermemory 218. The processor module 214 may be coupled to a communicationsinterface, such as a communication port 238, and a source of power, suchas a battery 234. Moreover, the battery 234 may be further coupled to abattery charger and/or regulator 236 to provide power to sensorelectronics 12 and/or charge the battery 234.

The program memory 216 may be implemented as a semi-static memory forstoring data, such as an identifier for a coupled sensor 10 (e.g., asensor identifier (ID)) and for storing code (also referred to asprogram code) to configure the ASIC 205 to perform one or more of theoperations/functions described herein. For example, the program code mayconfigure processor module 214 to process data streams or counts,filter, perform the calibration methods, perform fail-safe checking, andthe like.

The memory 218 may also be used to store information. For example, theprocessor module 214 including memory 218 may be used as the system'scache memory, where temporary storage is provided for recent sensor datareceived from the sensor. In some example implementations, the memorymay comprise memory storage components, such as read-only memory (ROM),random-access memory (RAM), dynamic-RAM, static-RAM, non-static RAM,easily erasable programmable read only memory (EEPROM), rewritable ROMs,flash memory, and the like.

The data storage memory 220 may be coupled to the processor module 214and may be configured to store a variety of sensor information. In someexample implementations, the data storage memory 220 stores one or moredays of continuous analyte sensor data. For example, the data storagememory may store 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20,and/or 30 (or more days) of continuous analyte sensor data received fromsensor 10. The stored sensor information may include one or more of thefollowing: a time stamp, raw sensor data (one or more raw analyteconcentration values), calibrated data, filtered data, transformedsensor data, and/or any other displayable sensor information,calibration information (e.g., reference BG values and/or priorcalibration information such as from factory calibration), sensordiagnostic information, and the like.

The user interface 222 may include a variety of interfaces, such as oneor more buttons 224, a liquid crystal display (LCD) 226, a vibrator 228,an audio transducer (e.g., speaker) 230, a backlight (not shown), and/orthe like. The components that comprise the user interface 222 mayprovide controls to interact with the user (e.g., the host). One or morebuttons 224 may allow, for example, toggle, menu selection, optionselection, status selection, yes/no response to on-screen questions, a“turn off” function (e.g., for an alarm), an “acknowledged” function(e.g., for an alarm), a reset, and/or the like. The LCD 226 may providethe user with, for example, visual data output. The audio transducer 230(e.g., speaker) may provide audible signals in response to triggering ofcertain alerts, such as present and/or predicted hyperglycemic andhypoglycemic conditions. In some example implementations, audiblesignals may be differentiated by tone, volume, duty cycle, pattern,duration, and/or the like. In some example implementations, the audiblesignal may be configured to be silenced (e.g., acknowledged or turnedoff) by pressing one or more buttons 224 on the sensor electronics 12and/or by signaling the sensor electronics 12 using a button orselection on a display device (e.g., key fob, cell phone, and/or thelike).

Although audio and vibratory alarms are described with respect to FIG.24, other alarming mechanisms may be used as well. For example, in someexample implementations, a tactile alarm is provided including a pokingmechanism configured to “poke” or physically contact the patient inresponse to one or more alarm conditions.

The battery 234 may be operatively connected to the processor module 214(and possibly other components of the sensor electronics 12) and providethe necessary power for the sensor electronics 12. In some exampleimplementations, the battery is a Lithium Manganese Dioxide battery,however any appropriately sized and powered battery can be used (e.g.,AAA, Nickel-cadmium, Zinc-carbon, Alkaline, Lithium, Nickel-metalhydride, Lithium-ion, Zinc-air, Zinc-mercury oxide, Silver-zinc, orhermetically-sealed). In some example implementations, the battery isrechargeable. In some example implementations, a plurality of batteriescan be used to power the system. In yet other implementations, thereceiver can be transcutaneously powered via an inductive coupling, forexample.

A battery charger and/or regulator 236 may be configured to receiveenergy from an internal and/or external charger. In some exampleimplementations, a battery regulator (or balancer) 236 regulates therecharging process by bleeding off excess charge current to allow allcells or batteries in the sensor electronics 12 to be fully chargedwithout overcharging other cells or batteries. In some exampleimplementations, the battery 234 (or batteries) is configured to becharged via an inductive and/or wireless charging pad, although anyother charging and/or power mechanism may be used as well.

One or more communication ports 238, also referred to as externalconnector(s), may be provided to allow communication with other devices,for example a PC communication (com) port can be provided to enablecommunication with systems that are separate from, or integral with, thesensor electronics 12. The communication port, for example, may comprisea serial (e.g., universal serial bus or “USB”) communication port, andallow for communicating with another computer system (e.g., PC, personaldigital assistant or “PDA,” server, or the like). In some exampleimplementations, the sensor electronics 12 is able to transmithistorical data to a PC or other computing device for retrospectiveanalysis by a patient and/or HCP. As another example of datatransmission, factory information may also be sent to the algorithm fromthe sensor or from a cloud data source.

The one or more communication ports 238 may further include a secondinput port 237 in which calibration data may be received, and an outputport 239 which may be employed to transmit calibrated data, or data tobe calibrated, to a receiver or mobile device. FIG. 24 illustrates theseaspects schematically. It will be understood that the ports may beseparated physically, but in alternative implementations a singlecommunication port may provide the functions of both the second inputport and the output port.

In some continuous analyte sensor systems, an on-skin portion of thesensor electronics may be simplified to minimize complexity and/or sizeof on-skin electronics, for example, providing only raw, calibrated,and/or filtered data to a display device configured to run calibrationand other algorithms required for displaying the sensor data. However,the sensor electronics 12 (e.g., via processor module 214) may 31 beimplemented to execute prospective algorithms used to generatetransformed sensor data and/or displayable sensor information,including, for example, algorithms that: evaluate a clinicalacceptability of reference and/or sensor data, evaluate calibration datafor best calibration based on inclusion criteria, evaluate a quality ofthe calibration, compare estimated analyte values with timecorresponding measured analyte values, analyze a variation of estimatedanalyte values, evaluate a stability of the sensor and/or sensor data,detect signal artifacts (noise), replace signal artifacts, determine arate of change and/or trend of the sensor data, perform dynamic andintelligent analyte value estimation, perform diagnostics on the sensorand/or sensor data, set modes of operation, evaluate the data foraberrancies, and/or the like.

Although separate data storage and program memories are shown in FIG.Z2, a variety of configurations may be used as well. For example, one ormore memories may be used to provide storage space to support dataprocessing and storage requirements at sensor electronics 12.

In a preferred embodiment, the analyte sensor is an implantable glucosesensor, such as described with reference to U.S. Pat. No. 6,001,067 andU.S. Patent Publication No. US-2005-0027463-A1. In another preferredembodiment, the analyte sensor is a transcutaneous glucose sensor, suchas described with reference to U.S. Patent Publication No.US-2006-0020187-A1. In still other embodiments, the sensor is configuredto be implanted in a host vessel or extracorporeally, such as isdescribed in U.S. Patent Publication No. US-2007-0027385-A1, U.S. PatentPublication No. US-2008-0119703-A1 (now abandoned), U.S. PatentPublication No. US-2008-0108942 A1 (now abandoned) and U.S. Pat. No.7,828,728. In one alternative embodiment, the continuous glucose sensorcomprises a transcutaneous sensor such as described in U.S. Pat. No.6,565,509 to Say et al., for example. In another alternative embodiment,the continuous glucose sensor comprises a subcutaneous sensor such asdescribed with reference to U.S. Pat. No. 6,579,690 to Bonnecaze et al.or U.S. Pat. No. 6,484,046 to Say et al., for example. In anotheralternative embodiment, the continuous glucose sensor comprises arefillable subcutaneous sensor such as described with reference to U.S.Pat. No. 6,512,939 to Colvin et al., for example. In another alternativeembodiment, the continuous glucose sensor comprises an intravascularsensor such as described with reference to U.S. Pat. No. 6,477,395 toSchulman et al., for example. In another alternative embodiment, thecontinuous glucose sensor comprises an intravascular sensor such asdescribed with reference to U.S. Pat. No. 6,424,847 to Mastrototaro etal.

FIG. 28 is an illustration of an example user interface 2802 thatincludes guidance 2804 to take two units of insulin to correct ahypoglycemic excursion.

FIG. 29 is an illustration of an example user interface 2902 thatincludes guidance 2804 to eat some carbohydrates

FIG. 30 is an illustration of an example user interface showing anotification that ingested carbohydrates are working, which may forexample be determined from a shift in a trend in a glucose concentrationlevel.

FIG. 31A is an illustration of a glucose excursion after a breakfastmeal. The example graph 3100 on FIG. 31A may be presented on a userinterface 3150 of a mobile device, tablet, or other computing device.The graph may include estimated glucose level (e.g., in mg/dL) on they-axis and time (e.g. hours or other time divisions such as schedulebreakfast/lunch/dinner) on the x-axis. The graph 3100 may include a lowglucose threshold 3102, a high glucose threshold 3104, and a pluralityof estimated glucose levels 3106 received from a glucose sensor, such asa continuous glucose monitor, that form a trend line 3108. The graph mayalso include a target 3110, which may for example be a midline betweenthe high threshold 3104 and low threshold 3102. It can be seen in FIG.31A that the trend line 3108 defined by the continuous glucose levels3106 has moved above the high glucose threshold 3104, which may forexample be a result of insufficient insulin bolus at a breakfast meal.FIG. 32A is an illustration of multiple trend lines (from multiple days)on a graph 3200 to show a distribution of trends 3202 and an average3204. The example graph 3200 on FIG. 31A may be presented as a userinterface 3201 of a device. A pattern of high glycemic excursions over anumber of days (or weeks or months) can drive up the patient's A1Clevel. An A1C test is a blood test, the result of which reflects theaverage blood sugar level for a time period (e.g., two to three months).The A1C test actually measures the percentage of hemoglobin (a proteinin red blood cells) that is glycated (coated with sugar).

FIG. 31B is an illustration of a glucose excursion after a breakfastmeal. The example graph 3101 of FIG. 31B may be presented on a userinterface 3151 of a mobile device, tablet, or other computing device.The graph 3101 may include the low glucose threshold 3102, a highglucose threshold 3104, and target 3010 shown in FIG. 31A. It can beseen in FIG. 31B that the trend line 3109 defined by the continuousglucose levels 3107 moved above the high glucose threshold 3104, buttimely delivery of a correction does of insulin (e.g., when theestimated blood glucose concentration level hit 202 mg/dL as indicatedby the example guidance) brought a later portion of the trend line 3111back below the high threshold 3104. FIG. 32B is an illustration ofmultiple trend lines (from multiple days) on a graph 3201 to show adistribution of trends 3203 and an average 3205. By comparing the graphshown on the user interface 3251 in FIG. 32B with the graph shown in theuser interface 3250 in FIG. 32A that the blood glucose is controlled(e.g., within a range defined by the high threshold 3104 and lowthreshold 3102) a larger amount of time, which results in a lower(better) A1C test result and correlates with better outcomes for thepatient.

FIG. 33 is an illustration of example glucose trends involvingintervention to address a hypoglycemic event. The graph 3300 may beshown on a user interface 3301. The comments (e.g., Actionable LowAlert, Positive Treatment Indication) are provided for the purpose ofillustration and explanation and may optionally be omitted from orincluded in the user interface. The user interface 3301 may show a lowglucose concentration threshold (e.g., 70 mg/dL) 3302, a high glucoseconcentration threshold (e.g., 200 mg/dL) 3304, and a target 3310graphed against a timeline (e.g., on the x-axis.) A first trend portion3306 shows a trend that progresses into a hypoglycemic event 3312 whereblood glucose is below the low threshold 3302. After the first trendportion, 3306, two trend scenarios 3114, 3116 are illustrated withdiverging trend lines. In a first scenario is evident from an unstabletrend 3114, the patient consumes carbohydrates to treat the hypoglycemicevent, which resolves the low, but the glucose trend “rebounds” into ahyperglycemic excursion 3118, which can be caused by excessiveconsumption of fast carbohydrates, or a Somogyi effect caused by releaseof glycogen by the body to treat the low. Continuing with the firstscenario trend 3114, the hyperglycemic excursion 3118 is treated withinsulin (guidance could optionally be shown in the UI, but is not shownin FIG. 33), which leads to another hypoglycemic event 3120, whichrebounds into another hyperglycemic event.

A second scenario is represented by a more stable trend 3116. In anexample, a decision support system calculates (or determines from amodel) that a projected low glucose level is imminent. The systemcalculates guidance 3350 and a time 3352 to deliver the guidance. Theguidance 3350 may, for example, include an instruction to eat an amount(e.g., 30 grams) of carbohydrates (as illustrated on the user interface3351 of the device 3352 shown in FIG. 33). The determination (e.g.,calculation) of guidance may for example take into account the amount ofinsulin on board (IOB), the trend (e.g. rate of change of blood glucoseor 2^(nd) or 3^(rd) derivatives of blood glucose), the insulinsensitivity of the patient, or the carbohydrate sensitivity of thepatient, all of which may be calculated by the system, determined from amodel, or received from a user. In some examples, the guidance mayspecify a time or time window (not shown) to consume carbohydrates(e.g., “in the next 5 minutes”), and the guidance may also specify ordifferentiate (not shown) slow (e.g., complex starches or a blend ofcarbohydrates and fats/proteins), fast carbohydrates (e.g. glucosetablets or maple syrup or other high-sugar foods), or other foods. Insome examples, a hypoglycemic event may be avoided by the timelyconsumption of carbohydrates. In the illustrated example, thehypoglycemic event still occurs, but carbohydrates already on board (dueto the timely delivery of guidance) enter the bloodstream and resolvethe hypoglycemic event. Additional guidance (“Carbs Working”) guidancemay be delivered during the hypoglycemic event to assure the patientthat no further action (e.g., consumption of additional carbohydrates)is necessary. As shown in FIG. 33, the timely delivery of guidance, andaction thereon, may avoid the rebound and oscillating hypoglycemicevents and hyperglycemic excursions.

FIGS. 34-37 are illustrations of an example user interface on a device.FIG. 34 shows a user interface 3401 showing fields for an estimatedblood glucose value (205 mg/Dl) 3402 and trend (arrow up around thenumber 205) 3404, insulin on board 3406, a time 3416 and amount 3418 fora last fasting insulin dose, a trend chart 3408 showing a high threshold3410, a low threshold 3412, and a trend line 3414. Pressing the boluscalculator button 3420 may bring up the bolus calculator screen shown inFIG. 35. The bolus calculator interface 3501 may include an amount ofcarbohydrates 3502, a glucose concentration level 3504, insulin on board3406, and a trend 3508. The bolus calculator application may use thisinformation to determine a recommended insulin dose 3510. In an example,the bolus calculator interface 3501 may include an additional fieldwhere a percentage (e.g., 70% or 150%) may be entered by a user, and theinsulin will be calculated as a percentage of the recommended insulin toallow a user to use their judgment to make adjustments to account forthe impact of exercise, illness, stress, or other factors. In someexamples, the interface 3501 may also display “Carbs on Board” inaddition to insulin on board as a convenience for the user to enablebalancing or awareness of both carbohydrates and insulin. Selecting theglucose value 3512 in the interface 3501 may bring up a glucoseinterface 3601 shown in FIG. 36, which may allow a user to enter aglucose value in a blood glucose field 3602 and may allow a user to see,or edit, a correction factor 3604, target glucose concentration level3606, and correction dose 3608. The interface 3601 may also show a CGMsensor glucose reading 3610, which may be useful for comparison to ablood glucose (e.g., finger stick) reading. Selecting a portion of alast acting dose field 3418 on the user interface 3401 shown in FIG. 34may bring up a Last Dose interface 3701 which may allow a user to entervalues in a last dose amount field 3702 or a last dose time field 3704and may optionally show or allow a user to edit an insulin action time3706 or an insulin on board amount 3708.

In some examples, a decision support system for determining guidance andtiming of guidance, such as the system 100 or any of the other suitablesystems described herein, is configured to modify its operation based ona disease state of the host. For example, when the decision supportsystem is used by a host having Type I diabetes, the decision supportsystem may be configured to respond differently when the hot's diseasestate indicates that the host is in a “honeymoon” period during whichthe host's pancreas still generates some insulin than at a more advanceddisease stage in which the host's pancreas makes less or sometimes noinsulin.

In another example, the decision support system can be configured tobase the guidance, timing of guidance, and other factors on the stagesof Type II diabetes. Type II diabetes has distinct stages during whichthe decision support needs of the host are different. Different stagesof Type II diabetes can be characterized by different courses oftreatment, such as a prediabetic stage, an oral medication stage, anoral medication and basal insulin stage, a multiple daily injection(MDI) stage, etc.

When the host's disease state indicates these different stages, thedecision support needs of the host may be different and the decisionsupport system may, accordingly, behave differently. For example, whenthe host is in the prediabetic stage, the host's ability to processinsulin may be impaired, however, the host may be able to obtainacceptable blood glucose concentration outcomes with a course oftreatment involving management of diet and exercise. Accordingly, whenthe host's disease state indicates a prediabetic stage, the decisionsupport system may be configured to emphasize functions related to mealmemory and management as well as exercise and physical activity. Forexample, the decision support system may be configured to provideguidance as described herein related to the nutritional content (e.g.,carbohydrate count) of the user's meals. The decision support system mayalso be configured to provide guidance related to exercise such as, forexample, guidance that advises the host to make a dietary or exercisechange as described herein.

When the host's disease stage indicates an oral medication stage, thefocus of the decision support system may shift to emphasize compliancewith the host's medication treatment. For example, the decision supportsystem may provide guidance and/or insights reminding the host to takehis or her medication. The guidance and/or insights, in some examples,provide the host with a description of the benefits of taking themedication, for example, to motivate the user to take the medication onschedule. In some examples, the decision support system configures thetiming of guidance or insights to correspond to the time when the hostis scheduled to receive an oral medication. In this way guidance orinsights can include a reminder for the host to take his or her oralmedication at the time that the medication should be taken. In someexamples described herein, the messaging frequency (e.g., frequency ofguidance and/or insight) is modified based on factors such as the hostor other user's engagement stage. When the frequency of guidance and/orinsights is limited, the decision support system may prioritize guidanceand/or insights based on the disease stage. For example, in an oralmedication stage, the decision support system may provide the host withguidance and/or insights related to diet and exercise but may adjust thepriority of guidance and/or insights to include insights related tomedication compliance, for example, at the time that medication is to betaken.

When the host's disease stage indicates insulin usage, such as basal orMDI treatments, the decision support system may configure guidance,insight, and/or the timing to emphasis titration of a basal or bolusinsulin doses. For example, the decision support system may increase themessaging frequency of messages or guidance related to detecting anddisplaying blood glucose patterns. If the host is receiving MDItreatments, the decision support system may provide guidance and/orinsight related to bolus calculation and meal planning, for example, asdescribed herein.

In some examples, a decision support system can modify the insight,guidance, and/or the timing thereof as the disease stage of a hostchanges. FIG. 39 is a flowchart showing one example of a process flow3900 that can be executed by a decision support system to change inresponse to changes in the disease stage of the host. At step 3902, thedecision support system receives an indication of a host disease state.This can occur in one or more of a number of different ways. In someexamples, a user device 256 (FIG. 17), display device 14-20 (FIG. 23) orother suitable device provides a user interface including a set-upwizard feature. When executed, the set-up wizard may prompt the host orother user via a user interface to provide data regarding the host'sdisease state, which may be related to Type II diabetes or anothercondition. For example, the host or other user may indicate treatmentsthat the host is receiving (e.g., diet and exercise, oral medications,basal insulin plus oral medication, basal insulin plus MDI, etc.).

In some examples, the decision support system considers various otherinputs describing the host to determine the hosts disease state.Referring again to FIG. 2B, the physiology model 112 may be used togenerate a disease state for the host using, for example, the inputsshown in FIG. 2B.

At step 3904, the decision support system determines if the host diseasestate indicates a first disease stage, such as a prediabetic stage orother stage for Type II diabetes, as described herein. If yes, then thedecision support system is configured for the first disease stage atstep 3906, for example, as described herein. If first disease stage isnot indicated, the decision support system determines at step 3908whether a second disease stage is indicated. If yes, then the decisionsupport system is configured for the second disease stage at step 3910,for example, as described herein. The process flow 3900 may continue fora number of disease stages (indicated as “N” in FIG. 36). For example,the decision support system determines at step 3908 whether an Nthdisease stage is indicated. If yes, then the decision support system isconfigured for the Nth disease stage at step 3912. After configuring thedecision support for an indicated disease stage at steps 3906, 3910,3912, etc., the decision support system may operate in the generatedconfiguration and may await a next indication of the host's diseasestage at operation 3902.

Each of these non-limiting examples can stand on its own or can becombined in various permutations or combinations with one or more of theother examples.

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” Such examples can include elements in addition tothose shown or described. However, the present inventors alsocontemplate examples in which only those elements shown or described areprovided. Moreover, the present inventors also contemplate examplesusing any combination or permutation of those elements shown ordescribed (or one or more aspects thereof), either with respect to aparticular example (or one or more aspects thereof), or with respect toother examples (or one or more aspects thereof) shown or describedherein.

In the event of inconsistent usages between this document and anydocuments so incorporated by reference, the usage in this documentcontrols.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In this document, the terms “including” and “inwhich” are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, composition, formulation, or process that includes elements inaddition to those listed after such a term in a claim are still deemedto fall within the scope of that claim. Moreover, in the followingclaims, the terms “first,” “second,” and “third,” etc. are used merelyas labels, and are not intended to impose numerical requirements ontheir objects.

Geometric terms, such as “parallel”, “perpendicular”, “round”, or“square”, are not intended to require absolute mathematical precision,unless the context indicates otherwise. Instead, such geometric termsallow for variations due to manufacturing or equivalent functions. Forexample, if an element is described as “round” or “generally round”, acomponent that is not precisely circular (e.g., one that is slightlyoblong or is a many-sided polygon) is still encompassed by thisdescription.

Method examples described herein can be machine or computer-implementedat least in part. Some examples can include a computer-readable mediumor machine-readable medium encoded with instructions operable toconfigure an electronic device to perform methods as described in theabove examples. An implementation of such methods can include code, suchas microcode, assembly language code, a higher-level language code, orthe like. Such code can include computer readable instructions forperforming various methods. The code may form portions of computerprogram products. Further, in an example, the code can be tangiblystored on one or more volatile, non-transitory, or non-volatile tangiblecomputer-readable media, such as during execution or at other times.Examples of these tangible computer-readable media can include, but arenot limited to, hard disks, removable magnetic disks, removable opticaldisks (e.g., compact disks and digital video disks), magnetic cassettes,memory cards or sticks, random access memories (RAMs), read onlymemories (ROMs), and the like.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or moreaspects thereof) may be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to complywith 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain thenature of the technical disclosure. It is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims. Also, in the above Detailed Description,various features may be grouped together to streamline the disclosure.This should not be interpreted as intending that an unclaimed disclosedfeature is essential to any claim. Rather, inventive subject matter maylie in less than all features of a particular disclosed embodiment.Thus, the following claims are hereby incorporated into the DetailedDescription as examples or embodiments, with each claim standing on itsown as a separate embodiment, and it is contemplated that suchembodiments can be combined with each other in various combinations orpermutations. The scope of the invention should be determined withreference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

What is claimed is:
 1. A system comprising: a glucose concentrationsensor configured to detect a host glucose concentration; acommunication circuit configured to receive the host glucoseconcentration from the glucose concentration sensor; a memory circuitincluding a stored model; and a processor configured to: accessing adatum associated with a host; determining a state of the host using thedatum; determining a guidance message based at least in part on thedetermined state; selecting a time for providing the guidance message;and providing the guidance message through a user interface at theselected time.
 2. The system of claim 1, wherein the time is calculatedto enable intervention prior to a transition of the host to anundesirable physiologic state.
 3. The system of claim 1, whereindetermining the guidance message is based at least in part on apersonalized behavior model of the host, and wherein the time iscalculated to be useful to the host in therapeutic management ofdiabetes.
 4. The system of claim 1, wherein the determining of the stateis based at least in part on a patient physiology model and a patientbehavioral model.
 5. A method of delivering physiologic glucoseconcentration management guidance comprising: measuring, determining, orreceiving a first real-time datum associated with a patient; determininga state the patient is in using at least in part a model and the firstreal-time datum; determining a personalized guidance message, whereinthe guidance message is based at least in part on the determined state;and providing the determined personalized guidance message through auser interface at a time calculated to enable intervention prior to atransition to an undesirable physiologic state.
 6. The method of claim5, wherein determining a guidance message is further based on a timingof the determining the guidance message or a time associated with thedetermined state.
 7. The method of claim 5, wherein the model includes astate indicative of a convenience or availability of the patient toparticipate in an intervention.
 8. The method of claim 5, wherein theguidance message is based at least in part on a projected transition tothe undesirable physiologic state.
 9. The method of claim 8, wherein theguidance message is based at least in part on a determination that aprojected transition from a present state to a projected state is alow-probability transition.
 10. The method of claim 5, wherein the modelincludes a patient physiology model, and determining a state the patientis based at least on applying the first real-time datum to the patientphysiology model.
 11. The method of claim 10, wherein the model furtherincludes a behavior model.
 12. The method of claim 11, wherein thebehavior model is based on a machine-learned characteristic of thepatient, the machine-learned characteristic based on a behavioral orcontextual pattern.
 13. The method of claim 11, wherein the behaviormodel is based on a set of one or more steps determined to be likely tobe performed by the patient.
 14. The method of claim 11, wherein thebehavior model is based on a set of one or more objectives determined tobe likely attainable by the patient.
 15. The method of claim 11, whereinthe behavior model is a pattern.
 16. The method of claim 11, wherein thepatient physiology model is based on a physiological pattern and thebehavior model is based on a behavioral pattern.
 17. The method of claim16, wherein the first real-time datum indicates a deviation from anexpected behavioral pattern.
 18. The method of claim 17, wherein thebehavior model indicates a tendency to over correct at a meal associatedwith a meal time, the first real-time datum indicates that a mealtime isimminent, and the guidance message corresponds to a lessenedovercorrection at the mealtime.
 19. The method of claim 17, wherein thebehavioral pattern includes a long-term behavioral pattern based onlong-term patterns of behavior and a short-term behavioral patternassociated with current behavior.
 20. The method of claim 19, whereinthe behavior model is based on the long-term behavioral pattern and isfurther based on the short-term behavioral pattern.
 21. The method ofclaim 20, wherein the short-term behavioral pattern is based on one ormore selected from the group consisting of: engagement with mobiledevice, accelerometer data, frequency of checking glucose concentration,calendar data, and combinations of these.
 22. The method of claim 11,wherein determining a state is further based on a measurement model. 23.The method of claim 22, wherein the measurement model is based on acontinuous glucose concentration monitoring system associated with thepatient.
 24. The method of claim 23, further comprising measuringglucose concentration data subsequent to the determining a guidancemessage and using the measured subsequent data to improve one or more ofthe models.
 25. The method of claim 24, wherein the glucoseconcentration data measured subsequent to the determining is fed back toa measurement model or the behavior model or the patient physiologymodel, or to a combination thereof.
 26. The method of claim 5, whereinthe model includes a pattern selected from the group consisting of: aphysiological pattern, a contextual pattern, or a behavioral pattern, ora combination of these patterns.
 27. The method of claim 26, wherein thephysiological pattern is based on a physiology model.
 28. The method ofclaim 5, wherein the model is a based on a combination of patternsselected from the group consisting of: a physiological pattern, acontextual pattern, or a behavioral pattern.
 29. The method of claim 5,wherein the determining a guidance message further comprises determiningmultiple guidance messages based on the state and the first real-timedatum and selecting one of the determined multiple guidance messagesfurther based on the state and the first real-time datum.
 30. The methodof claim 29, wherein the selecting is further based on a ranking scheme,a prioritization scheme, or based on a comparing of the multipleguidance messages to one or more associated thresholds.
 31. The methodof claim 5, further comprising determining an expected diabetic responseof the patient based on the state and the first real-time datum, andwherein the guidance message is personalized to the patient furtherbased on the expected diabetic response, wherein the patient is providedwith an actionable message calculated to move the expected diabeticresponse towards a desired diabetic response.
 32. The method of claim31, wherein the desired diabetic response is relative to the state andthe first real-time datum, and wherein the desired diabetic response isselected from the group consisting of: an improved diabetic response, apotential improved diabetic response, an idealized response, or anoptimized response.
 33. The method of claim 32, wherein the guidancemessage is based on a functional relationship between the expecteddiabetic response and a desired diabetic response.
 34. The method ofclaim 33, wherein the functional relationship is a difference between aglucose concentration level associated with the expected diabeticresponse and a glucose concentration level associated with the desireddiabetic response.
 35. The method of claim 34, wherein the glucoseconcentration level associated with the desired diabetic response is atarget glucose concentration level or a target glucose concentrationrange.
 36. The method of claim 33, wherein the functional relationshipis based on whether the expected diabetic response matches apredetermined condition associated with the desired diabetic response.37. The method of claim 36, wherein the predetermined condition is atarget glucose concentration level, a target glucose concentrationrange, a glucose concentration signal signature, or a rate of changeassociated with a glucose concentration level.
 38. The method of claim33, wherein the guidance message further comprises one or more reasonsassociated with the functional relationship, whereby the patient may beinformed as to why the guidance message is being rendered.
 39. Themethod of claim 5, wherein the guidance message includes an actionableprompt.
 40. The method of claim 39, wherein the guidance messageincludes an actionable prompt that is calculated to cause the patient'sglucose concentration level to move towards a target level or a targetrange.
 41. The method of claim 5, wherein the guidance message includesan affirmation of current actions associated with the patient.
 42. Themethod of claim 5, wherein the first real-time datum is measured,received, or determined by a smart phone.
 43. The method of claim 5,wherein the first real-time datum is measured, received, or determinedby a wearable device.
 44. The method of claim 5, wherein the firstreal-time datum is measured, received, or determined by a wearabledevice in combination with a smart phone.
 45. The method of claim 5,wherein the first real-time datum is measured, received, or determinedby an external device.
 46. The method of claim 45, wherein the externaldevice is an accelerometer.
 47. The method of claim 5, wherein the firstreal-time datum is a time of day, a characteristic or signature signalmeasured by an accelerometer, or a location determined by a GPS circuit.48. The method of claim 5, wherein the first real-time datum is a changeof state.
 49. The method of claim 48, wherein the change of state isdetected by a clock, an accelerometer, or a GPS circuit.
 50. The methodof claim 5, wherein the first real-time datum is a user request for adecision support prompt.
 51. The method of claim 5, wherein the firstreal-time datum is received from a continuous glucose concentrationmonitoring system.
 52. The method of claim 5, further comprisingmeasuring, determining, or receiving a second real-time datum, whereinthe second real-time datum is used in determining the state the patientis in.
 53. The method of claim 5, wherein providing the determinedpersonalized guidance message occurs at a time calculated to be usefulin management of a patient glucose concentration level.
 54. The methodof claim 5, wherein the state is a disease state describing a patientdisease stage.
 55. The method of claim 54, further comprising:measuring, determining, or receiving a second real-time datum indicativeof a second glucose concentration level; determining a second diseasestate describing a second patient disease stage at least in part byapplying the second datum to the model; and determining a secondguidance message based at least in part on the second disease state. 56.The method of claim 5, wherein the state is an engagement state, furthercomprising: determining a messaging frequency based at least in part onthe engagement state; and determining the time for providing thepersonalized guidance message based at least in part on the messagingfrequency.
 57. The method of claim 5, further comprising, during alearning period, receiving a learning datum, wherein determining thestate of the patient based at least in part on the learning datum.
 58. Amethod of determining and delivering a calculated guidance messagepersonalized and useful to a patient in therapeutic management of theirdiabetes, comprising: learning a personalized behavior model of thepatient; receiving a real-time datum; determining a personalizedguidance message to be rendered to the patient, the determining based atleast in part on the time of determination of the personalized guidancemessage and the personalized behavior model of the patient; anddetermining a delivery time to provide the personalized guidance messageusing the learned personalized behavior model, wherein the delivery timeis calculated to be useful to the patient in the therapeutic managementof his or her diabetes.
 59. The method of claim 58, wherein learning apersonalized behavior model of a patient includes machine learning afirst characteristic of the patient.
 60. The method of claim 59, whereinthe first characteristic is a pattern selected from the group consistingof: a physiological pattern, a contextual pattern, or a behavioralpattern, or a combination of these patterns.
 61. The method of claim 58,further comprising delivering the personalized guidance message at thedelivery time.
 62. A method of determining and rendering a calculatedguidance message personalized and useful to a patient in the therapeuticmanagement of their diabetes, comprising: measuring, determining, orreceiving a first real-time datum associated with the patient; using amodel, determining a state the patient is in, the determining based on apatient physiology model, a behavioral model, and a measurement model,the state determined by the patient physiology model and the behavioralmodel and the real-time datum; determining a guidance message, whereinthe guidance message is personalized to the patient based on at leastthe determined state, whereby the determined state and use of pluralmodels enables a personalization of the guidance message; and providingthe determined personalized guidance message via a user interface, suchthat the rendering occurs at a time calculated to be useful to thepatient in the therapeutic management of their diabetes.
 63. The methodof claim 62, wherein receiving a first real-time datum is a glucoseconcentration value.
 64. The method of claim 62, wherein receiving afirst real-time datum is a time of day.
 65. The method of claim 62,wherein the patient physiology model is a state model that includes oneor more of a glucose concentration state, an insulin-on-board state, andinsulin sensitivity state, an energy absorption state, or an energyexertion state.
 66. The method of claim 62, further comprising learningthe model from a set of input data.
 67. The method of claim 66, whereinthe set of input data includes one or more of clock time, time of day,glucose concentration level, insulin on board, patient activity, patientwellness, day of week, day of month, day of year, location, foodconsumed, or beverage consumed.
 68. The method of claim 66, furthercomprising determining a deviation from an expected state afterdelivering the personalized guidance message, and adapting the modelbased on additional input information.
 69. The method of claim 66,wherein the set of input data includes information received through auser interface.
 70. The method of claim 62, wherein providing thedetermined personalized guidance message includes rendering thepersonalized guidance message on a user interface.